I change controls fairly often, assuming the game lets me.
I pretty much completely remapped the entire control scheme for Thief Gold and Thief II. I changed all the buttons dedicated to controlling speed, remapped lean forward to an single key press, switched the number hotkeys for weapons so rope and moss arrows were easier to equip than fire and broadhead arrows, and set my lockpicks and compass to T and Y so I can access them much faster. There's more but the gist is that almost every control has been changed to something else.
I changed several of the default controls in Rainbow Six Seige to make certain actions easier. I set my mark button (for setting a waypoint my team can see) to a middle mouse click, allowing me to mark things while moving and aiming. I also changed my gadget button to one of the buttons on the side of my mouse, letting me use my gear without any hesitation.
Dishonored would be another one, specifically setting quick save to Tab and quick load to L.Alt, making save scumming a far easier thing to do.
Generally, any PC game where the main interact button is E I change to F, and every single game that has crouch mapped to C I immediately switch to L.Ctrl because I'm not an animal.
When playing with a controller (which I've only done for literally one game in the last year) I just go with whatever the default is.