Despite playing the game for over ten years now, and almost never DMing, I actually didn't have a character die on me until losing two in the most recent campaign (most recently last week, and before that a few months ago).
Ryal d'Orien fell victim to a mind flayer sorcerer who was holed up in Xen'drik with a bunch of minions. We kept assaulting his stronghold, running into something that we couldn't handle, and coming back, despite losing three of the four PCs in the process (one stayed around as a ghost).