pretty much every battle in Shadow of the Colossus.
A game where every level solely involves climbing a giant lumbering monster and figuring out how to kill it, and then clutching on, shoving a sword into it, pouring black blood out all over you?
ya.
my only issue with it is a couple of the bosses are similar in design, but they usually have at least a couple different elements that make it a different.
Edit: Shadow of the Colossus has been mentioned I see, but it bears mention again. When it comes to big bosses, SoC wins until Resistance 2 comes out, then we'll see.