The third or so boss from Luigi's Mansion. The giant boo, that splits into a bunch of smaller boos, and you have to freeze them all and... shatter them, or something? I hated that guy. I always, always got him down to just one or two boos before dying. And he starts off with a hundred. And I have to kill them all. Over. Again. Every time. The most frustrating part was that I know I can do it, because I've done it before! I beat this game when I was, like, ten years old! Why can't I beat it now?! WHY DO YOU KEEP KILLING ME, BOO?! GODDAMN IT, FREAKIN' HATE-
*Ahem* Yeeeaaah... Anyway, that's the only boss I can ever recall having trouble with that wasn't solved by just endlessly throwing myself at them. I never finished Super Mario Sunshine, either... but as I recall, that's not because I couldn't beat one of the bosses but because the game glitched out and the last level wouldn't open or... something. Never figured out what was up with that.
And then there was the first time I played Fallout: New Vegas, and ended up messing with the Legion when I was really early-game, so they kept sending assassins after me. Not really a boss, and I usually took care of them after a few tries and some creative use of the landscape, but it still got annoying fast. But I have a habit of getting in over my head with Bethesda games. It's fun, to try and find your way out of an encounter you have no business being in at your level.
Ooh, though I beat him eventually, I did have trouble with Deus Ex:HR and the battle with Jaron Namir because... yeah, I fell for the upgraded chip thing. I knew it'd screw me over, but I figured the game would force you to take it one point or another, so... thought I'd just get it over with. Turns out, for once, a game let you make a choice and then didn't immediately nullify any consequences it might have. Won that battle by constantly moving around and getting in potshots when he was jumping over the walls. Turns out the guy's aim is awful. Still though, not a fun (Or short) battle, when your Jensen's made of glass and all you've got is a sniper rifle and all those tranquilizer darts you've been stockpiling.