Strages

I actually have a slightly better fix for this. It is similar to that mentioned above, but with an extra step. Delete settings.cfg, start the game and set everything as you like (joystick axes, etc.). Now, close the game and navigate to your KSP root folder. Set settings.cfg to "Read-Only" (right-click->properties). Copy settings.cfg into the Launcher_data folder, delete the existing settings.cfg.bak, and rename the settings file to settings.cfg.bak. This will ensure it is "Read-only" as well. The advantage of this method is you never need to redo any settings, ever. The caveat, however, is that starting the game up without your usual joystick attached (powered on in the case of the XBox controller), you won't be able to click any of the items on the main menu. This will serve as a reminder that you need to attach/power on your controller prior to starting the game. Alt+tab, close the game, attach your preferred controller, restart the game, and everything is as usual - no need to reset any controls, graphics, etc.

Are you using TextureReplacer? If so, downgrade it to the second most recent version (1.5.10) - I had been having the same issues and downgrading made them all go away. If you can't find the right version, I can provide it.