The "Hell" level at the end of Doukutsu Monogatari (did I spell that right?). Hard stuff. I'm sure there was a boss in there somewhere, but I couldn't even get to it. =[
The "Weapons" from FF7. Obligatory. The desert and underwater ones. Ugh.
I also remember fighting a boss from FFX-2 for about an hour and a half straight. Wasn't really hard, just tedious. Honestly, though, I'd rarely consider RPG bosses 'hard'. Hard should be reserved for those bosses that require inhuman reflexes and skill, not simply gaining more levels.