In Xenosaga 2 after defeating one of those Erde Kaiser bosses I didn't save and ran into another creepy optional boss and died. The Erde Kaiser wasn't a difficult fight but it was a pain in the a.

FFXII I lost count of the number of times my game stalled after a bout of levelling.

FFX getting killed by a Marlboro in the Omega Ruins after gaining 80+ Sphere levels and several items required for status effect nulling slots on weapons.