Disclaimer:
This method is my personal way on how te become OP in greed mode.
There might be different methods out there but I've found that this is the easiest one yet.
If you have a suggestion on how to improve the guide then feel free to leave a comment.
Notable suggestions will be added and I'll reply to your comment with a thank you.

Maggie

Maggie excels for 2 reasons: 4 hearts of health and the yum yum heart. This will allow you to get a nice headstart and makes it easier to abuse the blood donation machine.




Samson

While Samson only has 3 hearts and no regen, he still makes this method really easy though a bit more time consuming. Using the blood donation machine will increase your damage. Clearing waves will become very easy giving you some starter coins straight off the bat.


What about the other characters?

Technically you can use any character to do this as long as the character has health.
Red hearts are the best and the more your character has the easier and less time consuming this'll be.

It's possible to do this as blue baby but you better make damn sure the shop sells blue hearts! These are priced at 5 coins each, making this method nearly impossible with blue baby.
You'll need some extreme luck to pull this off.

As for the lost you'll need extreme luck to get the holy mantle or the rune of algiz (resistance) as your first item. You're better off trying it the old fashioned way if you're playing as the lost.

Start a greed run with your character of choice and rush into the shop to check for a blood donation machine AND a cycle machine. If both aren't there you can reset. Complete the following steps to win the game.


1) Keep pumping health into the machine for coins.
2) Replenish your health by buying hearts from the store.
3) Have the blood donation machine explode into an IV bag.




Once you get the IV bag you're set for the rest for the run. If you get the blood bag instead then unfortunately you'll have to reset.

You might've figured this out by now. Just to be safe here are the next steps you need to take to become a powerhouse and kill anything in just a split second.

1) Use the IV bag to get money
2) Use money to replenish health when it gets low
3) Use leftover coins to buy upgrades from the store.

Rinse and repeat till you're satisfied. Recyle store items you don't want with the recycle machine.

Certain items can turn this from a time consuming thing to a brisk walk in the park. Keep an eye out for the following shop items and buy them right away.


The piggy bank


When picked up you'll get 3 extra coins and whenever you get hurt you'll generate 1 or 2 coins.
This guarantees you a minimum of 3 coins per IV bag usage. You'll be able to buy a red heart by just spending half a heart on your IV bag.
This means you can get back to max health really fast while amassing a ton of coins.


The bloody penny

Unlock this trinket by beating the chest with Samson.
If the shop's selling trinkets keep buying them till you get the bloody penny. For every coin you pickup you'll have a chance to spawn half a red heart when you're holding this trinket.
This'll make you a self sustaining money and heart machine, allowing you to stop buying red hearts from the store and just pick up the spawned red hearts you get from picking up coins.



The swallowed penny


Unlock this trinket by beating challenge #15.
While not as good as the bloody penny, this trinket will drop one or two coins whenever you get damaged. You'll still have to buy hearts from the store, but you're guaranteed more coins.
It's worth buying this trinket as you're trying to get the bloody penny.
This trinket also synergizes greatly with the humbleing bundle!



Isaac's Heart


Unlocked by defeating Isaac with the Lost.
This item will allow you to use the blood donation machine and IV bag without losing any health.
This will negate the need for red hearts and will allow you to generate infinite coins regardless of your health.



Maggy's bow


Unlocked by beating boss rush with Maggy.
This item will double the healing you get from red hearts.
This makes getting your health back super easy.



Health items


Anything that gives you more health means it'll be easier to generate more coins.



Humbleing bundle


You'll get twice the amount from all regular coin and heart drops. Speeds up the proces greatly!



PHD


PHD makes all pill effects either positive or neutral, gives you a random pill and heals you for two hearts.
A hidden effect is that it randomly adds 0, 1, or 2 coins to the payout every time you use the Blood Donation Machine or IV Bag. Combine this with a full health pill and you get a quick heal and easy money.


The fanny pack


This item has a chance to generate a coin, bomb, key or heart pickup when you get damaged.
Not as great as the abovementioned items but worth a spot.



The car battery


This item will activate your space bar item twice on each use. Since the IV bag has no charge you'll end up spending 1 heart instead of half a heart at once. Simply put, you'll activate the item twice with one button press. Early on this isn't favorable but once you get one or two of the above mentioned items this will become a very useful pickup.

Eventually all good things come to an end. The shop'll start only selling regular pickups (keys, bombs, hearts, pills, trinket) and the milk carton (Breakfast) health pickup.

Once this happens you've depleted the shop item pool and it'll be time to move on and complete your greed mode run. Make sure to max yourself out with 99 coins for the greed fight!

The greed coin machine explodes at 109 coins. So filling it beyond this will yield no further unlocks. This might be updated in the future but so far that's only speculation.

Here's the short version for all you busy folks.

1) Pick either Maggie or Samson.
2) Reset until your shop has a blood donation machine AND a recycle machine
3) Use the blood machine until it explodes and gives you a IV bag.
4) Buy red hearts to keep your health maxed out.
5) Use excess money to buy other items.
6) Get piggy bank + blood penny to speed things up
7) Recycle the store if needed

Thank you for reading my guide and hopefully you'll manage to pull this off easily.

If you got any suggestions or questions feel free to leave a comment.
Suggestions will be considered and the ones that are very significant will be added to the guide.


A big thanks to the following people who made suggestions to improve the guide!

Shadow_Spy
Sir_Corn
CapLaPorte
Gamesiarz
Burn1none