Probably several occurrences in Oblivion on the PC, when my mouse goes ape-shit and turns to the corners of the screen in the speed of annoyance caused by some in-dug gravel on the mouse-pad.
Inevitably, I left click and accidentally click outside of the game screen, bringing me out while Oblivion is trying to keep running, although I'm not in it.
When the computer tries get back to life, and I try get into Oblivion again, every thing's fucking frozen. Than I attempt CTRL+ALT+DEL, but there's only a 50% chance it'll work, or I'll have to reset the computer.
Worse, all the save will be automatically deleted, making all my efforts on leveling or getting by an annoying main quest a waste.
Needless to say, that always proves to be a pain for me.