It may seem strange but the biggest thief of performance that I've encountered is the Log system. Here's a couple of instances:

• It causes stuttering when the game runs for a long time as the log builds up. Making the game run slower and sometimes freeze all together.
  
• When a character is imprisoned and his character exploration menu is open, it causes the game to stutter heavily. I believe this is because it keeps writing the same message to the log, but I've not confirmed this. However, after turning off several messages this problem has disappeared completely.
  
• Whenever you open a menu the game will freeze or stutter and can sometimes crash all together. The menus that seem to stutter the most is the intrigue and minor titles menu.

All of these problems disappeared when I turned off all messages that were written to the log and also turned off several messages that don't provide me with any useful information. I cannot tell you exactly which messages have removed the stutter/lagg but I can tell you this: Turn off as many messages as you can. Any message that is turned on writes to the log and as the log builds up the game will stutter, freeze or crash.

Any message you find that isn't providing you with any useful information should be turned off. There are several ways of doing this. You can open options and go into message settings and start turning them off.
https://ck2.paradoxwikis.com/images/3/36/Message_settings.jpg

Or you can turn off messages that appear in High Priority Messages and Low Priority Messages during gameplay by right-clicking the title of the message and thereby opening the message settings menu for that specific message.

Despite this I end up having to reboot the game every 3-4 hours, but the more messages I turn off the better it seems to get.

I wish it was possible to turn off the log all together, but so far I do not know how. If anyone reading this knows, please message me.

Changing your settings.txt does not deactivate Achievements!

Go to: C:\Documents\Paradox Interactive\Crusader Kings II\settings.txt
And make the following changes:
shadows=no
dynamic_sound=no
mapRenderingOptions=
{
draw_terrain=yes
draw_water=no
draw_borders=yes
draw_trees=no
draw_rivers=no
draw_postfx=no
draw_sky=no
draw_bloom=no
draw_tooltips=yes
draw_hires_terrain=no
draw_citysprawl=no
}
disable_wikipedia_links=yes
low_res_textures=yes
context_music=no
province_embellishment=no
transparent_wastelands=yes
wasteland_adjacency_coloring=no

You can change these settings to whatever you prefer. The settings I provide you with here won't be pretty, but it'll perform. You might want to have rivers and terrain activated since they can help you make good military decisions. Maybe Water as well but Water is a very expensive aesthetic feature and does nothing for gameplay. There are mods that can replace Paradox's expensive water with simple textures for better performance. Achievements should still work with such a mod (since it only changes graphics).

Changing the low_res_textures option will break certain imprisonment textures, but like I said, it won't be pretty, but it'll perform.

Turn off the DLC's you don't need.

Turning off all music packages will reduce the load time of the game.

Despite running the game on a high-end graphics card installing a graphics mod that simplifies the graphics has improved performance a lot, to the point where I have a lot less if any lagg while playing on the map. I no longer have to restart the game every 4 hours to get acceptable performance. As long as the graphics mod you choose only modifies graphics you can still gain achievements. I'm using a mod that simplifies the terrain and replaces the water with simple blueish textures.

When you enter the Intrigue tab you can experience a great deal of lagg as the game attempts to load all your prisoners and filter them according to your filter settings. As an enormous empire this takes a long time. To counter this sort by Great House -> My Dynasty. That should net you the least amount of prisoners loaded in unless you've got a large dynasty and a lot of them in prison.

Foreigners -> Yes along with Rulers -> Yes is also an option.

Sadly you cannot have a filter for the "Known Plots" tab so to reduce lagg keep clearing out plots or activate auto stop. To prevent lagg when you don't need to see known plots make sure you exit the Intrigue menu with either the Prisoners or My Plots tab selected (otherwise the game will load every character with a known plot).

If you experience lagg after imprisoning someone with their character portrait open, press their portrait again to remove it or close the menu entirely.

There is no fix for this that I know of. Paradox has solved it in the past but then reverted the changes back to a lagging menu. If you experience this and know of a fix please message me.