The official instructions can be found at: http://sentinelsdigital.com/variants.html
For the unlocks below, I'll be guiding you through how to actually achieve them in game. The unlock conditions are known, but figuring out how to do it is often the difficult part.

Generally, deck control will help you out the most. Visionary, Wraith with Infrared Eyepiece, Tachyon for Fleet of Foot (to get extra cards), and Argent Adept, (who gives extra card plays, draws, shields, and damage buffs) will help your heroes get set up for the specific situations you may need to pull off. Most of this information has been discussed in this forum and others in the fanbase.

Multiplayer is now out, and some people may want to unlock these variants with their friends. You should know that unlocking variants IS possible in multiplayer.

All the Villain variants require a lot of setup, and if you get a team of people together who fulfill those conditions together, you all get the variant.

For the hero variant cards, it's a little different. If you want it, you have to be the person playing the base version of that hero character to get their variant. Since a couple unlock conditions require getting that hero incapacitated, your team may not want to wait through a game just so you can incapacitate your hero when they won't get anything for it. I'd suggest doing Horus Ra and Dark Watch Mr Fixer in a single player game, alone.

Also, due to the above rule, America's Greatest Legacy is not currently unlockable in multiplayer.

Official Unlock Conditions: Defeat Ambuscade in Silver Gulch with no hero character cards over 9 HP and Legacy not on your team.

This one is fairly easy. Ambuscade is a fairly simple villain for most teams to defeat, and the environment can throw out lots of damage from the explosive barrels. If Ambuscade is at low health, and your heroes are above 9hp, just hit each other for a couple rounds before you finish him off. There's nothing wrong with incapacitating some of your heroes either. Easy peasy.

Global damage dealers like Ra, Tempest, Tachyon, and Expatriette can make this quite fun with damage flying everywhere, and Rook City Wraith can dig for those Explosive Barrels and play them early for a very short but massively damaging game.

Official Unlock Conditions: Defeat Baron Blade in Rook City with Expatriette using the card “Unload” to fire guns at least 3 times at Baron Blade to destroy him.

Expatriette has no card draw of her own, beyond skipping a turn or two, so the most difficult part of this scenario is getting her set up. Baron Blade is often one of the easier villains, Rook City is the most difficult environment, but it's manageable. A good team would include Tachyon for extra card draw, and environment control, Visionary to help mill Expat's deck and get at least 3 guns and an unload, and Legacy or Greatest Legacy to buff Expatriette's damage or give her more opportunities to deal the final blow with an Unload. Expatriette does good damage on her own, and a team of 3 or 4 should be sufficient. If you have trouble, add another damage dealer or environment controller like Tempest.

One thing to watch out for: Expatriette needs to shoot at least 3 times. If she kills Baron Blade with her first or second shot, you won't get the unlock. Playing Visionary's Twist the Ether on Expatriette will allow you to deal more or less damage per hit, letting you manipulate it so that her 3rd 4th or 5th shot takes out Blade.

If you don't have 3 guns out, and Blade is at low hp, it can also be done with just Pride and Prejudice. If you Unload, use Prejudice, and then use Pride, you have the option to use Prejudice a second time to deal damage a third time, thus filling the conditions for the unlock as long as the third shot takes him out

Official Unlock Conditions: The Operative herself deals damage that incapacitates Mr. Fixer in Rook City. Bloody Knuckles, any one Style, and no Tool must be in play.

This one is tricky because The Operative only hits highest hp hero targets, even with the only damaging one shot in Chairman's deck: Undivided Attention
The Chairman is a very difficult villain, and playing against him in Rook City is even worse.The good news is you don't have to win to get the unlock, as long as The Operative incaps Fixer. The difficulty comes in getting Fixer's setup out quickly, and then having him get picked off by The Operative before the whole team is taken out by a Hired Gun, or The Muscle.

Don't destroy Blighted Streets, because it increases The Operative's retaliation damage.
Never play a tool on Fixer. If he has one when he gets incapped, you can't get the unlock.
Playing with a 5 hero team is good, because the Operative deals H-2 retaliation damage.
If Fixer has Bloody Knuckles, Blighted Streets is in play, with the nemesis bonus, and Twist the Ether on Operative, she can do 8 damage to him in one hit.

If you're having trouble, try this team: Haka, Mr. Fixer, Tachyon, Wraith, and lastly Visionary or Legacy

Haka to eat the most annoying of the minions with Savage Mana, like the Crooked Cops and the Thieves. Don't let him eat everything indiscriminately though, you want to be able to keep destroying thugs so the Operative deals damage reliably.

Wraith to control the villain deck with Infrared Eyepiece, and to help Haka manage minions. Get the Infrared out first though.

Tachyon to hit everything at once, control the environment, help Fixer find his Bloody Knuckles, and best of all: play Synaptic Interruption. If you can keep Tachyon at highest HP, Operative will hit her, then she can redirect it to Mr Fixer. This way you can let Fixer get knocked down quickly without taking out your whole team first. Use normal Tachyon, Super Scientific Tachyon is too unpredictable

Legacy, or Greatest Legacy to provide damags buffs so your team can eat through thugs more quickly, and maybe to stall a little longer for you to get Fixer's style and Bloody Knuckles out. (Greatest Legacy if using the Synaptic Interruption strategy to keep Tachyon at high HP)

Visionary instead of Legacy if you're having trouble fishing for Mr Fixer's setup. She'll get him extra cards in no time, and she can also Twist the Ether on the Operative, increasing her damage to Fixer, and decreasing it to everyone else, plus she can sit in her Telekinetic Cocoon with Demoralization in play, reliably hitting all the thugs every turn.

(Thanks to Donner from > G forums for most of the advice in this section)

Official Unlock Conditions: Defeat GloomWeaver on his “Demon-God Incarnate” side using The Visionary. Telekinetic Cocoon must have been destroyed at the start of The Visionary’s turn.

Gloomweaver is a fairly simple villain most of the time. He has very little ongoing destruction, and what he does have, you can usually just choose to take the damage instead, and since that ongoing card is hopefully your Telekinetic Cocoon, Visionary won't get hurt. The hard part about this is actually flipping Gloomweaver. You may have noticed Gloomweaver almost never flips. He's just so easy to fight on his front side that we never see his back side. To do so, you need to fish for all 3 of his relics, and have them in play at the start of his turn.

A good team for this fight would include Legacy for tanking/healing, Rook City Wraith in Atlantis to fish for Pillars of Hercules, and play it. It will play Villain cards quickly, so he flips easier, and her Infrared Eyepiece will help find those relics and put them on top. The rest of your team should be reliable damage dealers to burst Gloomweaver so that Visionary can destroy her Cocoon at the beginning of her turn and play a damaging one-shot to finish him off.

A super easy but very time consuming way to get this unlock would be to incapacitate your whole team while Visionary sits in her Cocoon and powers up with card draws/extra damage from incapacitated powers until she has enough to destroy flipped Gloomweaver in one shot. Expatriette, Absolute Zero, and Fanatic each have a good incapacitated power for that, if you want to go that route. (All three of them incapacitated can add 5 damage/round, so technically, in about 18 rounds Visionary can do a full 92-93 damage, one shotting poor Gloomy)

Official Unlock Conditions: In the Realm of Discord, deal damage to both hero and villain targets with an Oblivion play that revealed two 4 spell icons. Expatriette must be on the team and Master of Magic must be in play.

This is another one where you don't have to win in order to get the unlock, so that makes things a little easier. The choice of villain doesn't matter either, so you can choose any villain that's easy to control. Many people use Ambuscade, or Gloomweaver for this since they're generally easy, and have very little ongoing or equipment destruction.
Then you want control of the top 2 cards of her deck, and maybe a little help getting Master of Magic and Oblivion out. Argent Adept has Vernal Sonata, which puts a card in the trash on top of the deck, and Tempest has Reclaim from the Deep, which does the exact same thing.

So, in this order: Visionary, Argent Adept, Tempest, Nightmist, Expatriette.
1. Visionary to help find Master of Magic and Oblivions for Nightmist, Vernal Sonata for Argent Adept, and Reclaim from the Deep for Tempest.
2. Argent Adept plays Vernal Sonata, Nightmist puts a 4 card on top of her deck.
3.Tempest plays Reclaim from the Deep, Nightmist puts a 4 card on top of her deck.
4. Nightmist plays Oblivion, revealing two 4's, and hits everything. Don't reduce or redirect all that hero damage! It needs to hit hero targets in order to count.
5. Expatriette sees this spectacle and is impressed, then invites Nightmist to the Dark Watch

Official Unlock Instructions: Defeat Apostate with damage dealt by Fanatic using the power on “Absolution.” Undaunted must be in play. Prayer of Desperation must have been played at some time after Fanatic was restored by Aegis of Resurrection.

No environment is required, so picking Insula Primalis or Silver Gulch is generally safe. Realm of Discord could also work, as long as you don't get Claustrophobic Delusions out for long. Fanatic needs 4 specific card plays in order to pull this off, and a good team to take out relics. Visionary or Argent Adept are great picks for helping her get set up and play specific cards. She'll do good damage to Apostate anyway with her nemesis bonus, just one more +1 damage bonus will have her doing 6 damage to Apostate with every base power use. Haka, Young Legacy, and Wraith are good choices to be relic destroyers.

As soon as you find them, she can play her Undaunted, Absolution, and Aegis of Resurrection anytime in the game, but shortly after all 3 are out and Prayer of Desperation is in hand, break the Aegis. Divine Sacrifice, Sacrosanct Martyr, or even another hero to focus her down are great ways to do that. Then play Prayer of Desperation, it doesn't have to be on her turn, Argent Adept can give her the play. Next opportunity you get, hit Apostate to 0 hp and no relics in play with her Absolution, and you got it.

Official Unlock Instructions: A member of The Ennead deals damage that incapacitates Ra. The Staff of Ra, Flame Barrier, Flesh of the Sun God, Living Conflagration, Solar Flare, and Wrathful Gaze must be in play.

You don't have to win this one, so that's nice, and the environment doesn't matter. Realm of Discord is probably the best environment for giving extra card plays to the heroes, hope for a Time Flies.
This one is really all about Ra, and getting as many of his ongoing cards into play as possible. (6 of them to be exact; Imbued Fire, Drawn to the Flame, and Blazing Tornado are not necessary.) The best heroes to help him are probably Visionary, Argent Adept, and Nightmist (with her card Enlightenment)

Start it up, and give Ra card draws and extra plays, The Ennead generally do lots of little pings of damage, which is great for burning down Ra quickly with the nemesis bonus. It's just a race to see if you can get all his stuff out before the Ennead finish him. Play Flesh of the Sun God earlier if the Ennead are doing damage too quickly, or Solar Flare earlier if they aren't.

If you're having trouble, remember to manipulate the Ennead's deck with Visionary and Nightmist (Astral Premonition comes in handy for this). Once Ra has Flesh of the Sun God in play, he can't take fire damage, and several of the Ennead's one shots deal fire. You definitely want to avoid Ancient Magics, as that will destroy all those ongoings you worked so hard to get into play, and The Grave Beckons will destroy a target with < 3 hp, and doesn't actually deal damage. It could destroy Ra without getting you an unlock if he happens to be low hp. Hunt for Elemental Storm, that does the most reliable damage to Ra.

The worst member of the Ennead for this scenario is Osiris, he makes the heroes discard cards and do self damage, and could cause Ra to incapacitate himself without the unlock. He should be the priority target.

Official Unlock Instructions: Defeat standard Spite. Then, defeat GloomWeaver by having 3 villain relics in the villain trash. At least two of the following must be in play: Cursed Acolyte, Profane Zealot, Chosen Disciple, or Ophidia the Deceiver. No Voodoo Pin may be in play.

There's 2 steps here, defeating a difficult villain, and then defeating an easy villain with very specific conditions. This unlock shouildn't be too hard though, if you have enough villain control. The environment doesn't matter, so Silver Gulch, Insula Primalis, or Realm of Discord are probably the best for both villains.

Many people have difficulty with Spite normally. so here's a good strategy for him.

3 Hero teams against Spite are generally the easiest, since it massively decreases the amount of damage reduction he has with "PL602 Compound Omicron" and the amount of ongoing/equipment cards you have to put back with "PL531 Compount Upsilon" (H-2 in both cases). The best hero team is probably Wraith, Tachyon, and Haka since they do plenty of damage, and can all decrease the amount of damage he deals and control his deck, possibly even taking him out before he flips. You can subsitute Tempest or Legacy for Haka if you need some healing along with good damage. I'll go over other good Spite strategies in the next section, since that's what it's all about.

After Spite is down, bring a full team to fight Gloomweaver, with all the deck control you can find, because you want to discard his relics, keep a few of his cultists out, and keep any voodoo pins from being in play after the last relic hits the discard pile.

So Dark Visionary for easy top deck control, Wraith for the same, but with lots of damage, Haka for Savage Mana to hold onto relics and Ground Pound, Legacy for the damage buffs to help destroy relics and for Heroic Interception, and Super Scientific Tachyon for damage prevention, lightspeed barrage to take out a relic, and her base power "Experiment" can take relics directly from Gloomy's deck and throw them into the trash.

You could switch Argent Adept in any of those positions for deck control and damage buffs, plus Cedistic Dissonance can destroy relics immediately.

(Thanks fo powerhound_2000 in these forums for most of the information in this section)

Official Unlock Condtions:
Defeat standard Spite and GloomWeaver. Then, do one of the following:

Defeat Spite: Agent of Gloom in Rook City on his “Broken Vessel” side with zero cards under the Safe House and five Victims in play;

???

We don't know the second unlock condtion yet, but this will be hard. We have the most difficult environment, against the most difficult villain yet released. (Iron Legacy, once he is released is probably the hardest overall.) and you do have to win. He also has a very specific set of instructions which are hard to achieve, at the rate Spite kills victims.

I haven't done this one myself, so I'll put 2 strategies others have suggested here, if one strategy doesn't work, use the other.


[GøR]Setback
Firstly, you want a team that can survive anything that Spite throws at you...I went with my OG team of Grandpa Legacy (extra powers are too op, and they will be pivotal to accomplishing the goal), Dark Visionary (Deck Manip for both Spite and Rook City, and the first half of the Can't Touch This Combo with Twist the Ether), Ra (For DPS with one shots and the Second half of the Can't Touch This Combo with Flesh of the Sun God's Power), and Wraith (More Deck Management and the true DPS of this team due to all the attacks she can throw with bonus damage).

(Note, for those who don't know the combo, if you play Twist the Ether on Spite, you can make all his damage fire damage, and if Ra uses the power on Flesh of the Sun God, all heroes can't be damaged by fire. Since Spite is the only villain target dealing damage, everyone is immune to it.)

The Second part to this strategy is simple...Flip Spite ASAP...which means taking any and all punishments for saving victims. Yes, even that stupid good samaritan and the helpful sidekick have to be saved instead of left out. The reason for this is simple: STOP SPITE FROM BECOMING UNMANAGABLE. You need to limit the drugs he has on his second side, and since 4 victims is pretty easy to manage to save to flip him, you wanna bum rush them into the safe house to make it so you're only dealing with 1 or two drugs. Ideally you wanna leave Spite with Demon's Kiss (just damage, and the combo will stop that), Upsilon (increased damage and bouncing cards back) or Omicron (Damage mitigation), as they are easy to manage. Mindphyre is also not a bad idea, but Tony Taurus is invaluable to manipulating Spite, so losing the environment each turn can be good or bad...also him blowing up Blighted Streets and getting a Forced Entry would not be nice at all. Do not leave Xi out, as losing 5 cards a turn can cause you to miss key cards for the combo and make this fight even harder.

So you flipped the Agent of Gloom, now what? Now, you gotta manage Spite to play more Victims and limit his damage even further while pulling those 4 guys out from under the safe house. Remember that pulling out victims from the safe house gets you free card plays, so use that to bulk up and wail on Spite. If the combo is in place, take time to make sure he has enough victims in play before going for a kill, and you'll get it for sure. Remember that Lab Raids are ok to leave, especially with the combo in place, as it is a dead draw for Spite that only does damage.

Some other minor tips to include: Cards that are good ideas to bounce if you are stuck with Upsilon include The Staff of Ra, Inspiring Presence, and fodder Ongoings/equipment such as Mass Levitation or Wrathful Gaze. In phase 1, focus on getting victims as Spite's plays, and remember that Rook City can help by way of Scum and Villainy, Blighted Streets and Twisting Back Alleys. Once flipped, get the Can't Touch This Combo up ASAP to limit damage (if you have it during phase 1, even better), then focus on preventing victims from dying by avoiding Forced Entry, Collateral Damage, and On The Prowl. I ended the game with pretty much every victim in play and my team in relatively good shape (Wraith was nearly dead, but it took a bit to get the cards for the combo so Spite was laying into her like no one's business) And finally as a last tip...once you do this challenge, never do it again XD.

Second, it may be worthwhile using Super Scientific Tachyon to use her power on Spite to try to get more victims out quickly




Mysti_Fogg
I used Legacy in the first slot (this position is important), Super Scientific Tachyon, Mr. Fixer, Wraith, and Dark Visionary.

Legacy is in the first slot so that if he gets out Inspiring Presence and Spite makes you pick up ongoing cards, you can pick up Inspiring presence and put it back out again and again to heal your crew and increase damage. Always hit Galvanize unless you get in a position to kill Spite too early.

Super Scientific Tachyon essentially gets to go twice each round using her special ability. Try to get out cards that allow others to draw cards and build up the Burst cards in your trash so that you can quickly hit Spite hard.

Mr. Fixer adapts easily to all circumstances, though I really liked the Hoist Chain for this run, along with either Grease Monkey or Tiger styles. The Grease Gun is also nice since it prevents Spite from dealing damage. When Spite starts making you dump your cards, you can also do things like put out the Tool Box that would have needed to be retrieved anyway and use Salvage to put all your equipment dumped into the trash into your hand instead.

Wraith uses her Infrared Eyepiece to look at the villain deck and put victims on top. When there are no victims, she can still dump cards that would kill victims or invade the safehouse into the villain trash. And between her Stun Bolt and Mr. Fixer's Hoise Chain, you can greatly reduce the damage done to your heroes.

Dark Visionary can back up Wraith's Eyepiece if you didn't find a victim the first time. And she can also use Suggestion to pull victims out of Spite's trash if he killed someone too quickly.

NOW, I will admit to "cheating" a bit on the drugs by hitting rewind. I'm not ashamed of this because I could beat the villain just fine in normal play, but the unlocks require setting up specific circumstances, and that's difficult. You want the last drug to flip to be the one that causes you to put ongoing cards back in your hand. If it comes out early, you're screwed because you won't be able to control the Villain deck as much and you'll likely kill all of your Heroes before you get Spite to flip.

Once you get Spite to flip, put a Safehouse Break In on top of his deck. By this point you want to have reduced him to under 30 hp: the less, the better. Hit him hard to finish him off in 2 or 3 rounds, and don't put any victims back in the Safehouse. Tachyon and Wraith are great for this