Hard to pin down just one, but a good one that comes to mind is Fable Anniversary edition, I've played the game so many times and know the story by heart, and pretty sure I've run every combo of weapon playstyle/good vs evil playthough but it always stays a game I can replay without fatigue or boredom.
Hearts of Iron 4 modded with Blackice is my ultimate comfort game. Its so chill to just sit back, play at a slow speed, and manage all the intricacies and micromanagement at my own speed.
When I want to relax and try to distract myself from physical pain, I play with balls, my balls.
But most of the time, I take the whole thing a little too sportiv and overdo it.
I play until they start to hurt, so I'm back to the Roots.