Poke'mon Red. I had 110 poke'mon, beat the elite four, had at least one poke'mon at level 100. Spent hundreds of hours on it probably. But got corrupted cos of Mew and Missengo.
Had to call Nintendo, they did something to the cart or possibly nothing who knows, sent it back but save was still gone. Never spent that long on one game since. This was in the 90's obviously long ass time ago.
Fallout 3 was super-buggy on 360. I lost hours of progress when the game crashed. New Vegas was still buggy so same thing happened but not as much. I got both GOTY on PC recently they seem more stable. I assume by now they've dealt with all that crap.
Flashdrive, damn you have one of those models with no HD space. After swapping to PS3 this year and also PC I can say my gaming experience is at least 20% cooler. The 360 gave me tonnes of freezes and the like.