I hate boss battles. I'm terrible at them :D I guess that's why I tend to think that most bosses I managed to defeat could not have been all that tough. But let's try:
Star Trek Voyager: Elite Force- I don't remember what the fucker at the end was called, but he was tough as nails. It took me forever to defeat him. I think I was in some kind of berserker rage by the tme I finally did it.
Prince of Persia: Warrior Within- that game was hard all around, and pretty much every boss fight along the way cost me a lot.
Tomator in Lost Vikings- Yeah, I know. Not exactly one of the usually brought up epic boss battles. But for me ot was possibly the most tense. The whole last level is very difficult, so knowing, while fighting Tomator at the very end, that if I fuck up and even one of the vikings dies I'll have to do the whole level again (for the 437 time or something like that) made it feel like really a matter of life and death.
I've heard some people say that Kreya in KotOR II and Lucifer in Painkiller were tough, but I actually don't remember them as so bad.
The ones who defeated me:
Demon Stone- the final boss is just a damage sponge the kinds of which I've rarely seen. Two of the three characters you control in the game (and switch between on the fly) are almost entirely useless in this fight. It just seems to go on forever, with waves and waves of minions in between very short fights with the actuall boss. But what really defeated me was the unskipable cut-scenes. There is one before the fight, and one in the middle (hell they may be even more I never got to), and I just got so sick os watching them I finally gave up.
Dungeons of Dredmor- I only got to Lord Dredmor once, and it wasn't even a close fight. He killed me in two hits. If it was any closer, I'd try again, but as it was, I decided it would be a terrible waste of time.
FTL- Lady Luck doesn't love me, so a game where so much depends on random chance is a tough nut for me. I don;t think it was even possible for me to beat the final boss with the ship, crew and weapons I got. Worst of all, he's the "it's not even my final form" kind of boss. I managed to survive two rounds with him, but eventually I went down with the ship. I felt bad about it too. After all the Star Trek and Firefly etc. I've watched, you'd think I'd be a better captain, right?
Vampire The Masqerade Redemption: Not many people seem to mention this final boss among the tough ones. I guess I just fucked up, but no matter how much I try, and how, I can't even get through the first stage of this fight. Maybe I chose my skills all wrong, maybe I've got the wrong equipment, maybe I just suck (pun not intended). And once I learned that there is whole another stage to this fight, I just gave up. Way, way to much time spent on it already.
And lots, lots of others I might describe in detail later, in case the "I suck at video games" point needs even more clarification :D