I remember beating the game on normal (she wasn't a pain then), then going to very hard right after (not my smartest choice), got up to Alma on said difficulty... couldn't beat her for an entire year and 4 broken xbox controllers later. :-/
No one else in any other game gave me THAT much trouble.
Honorable mention, who came close (different genre): the second to last boss in Phantasy Star 2. Super pain for me... then again, that was a hard RPG in general.
to my knowledge the hardest boss was the sleeper (Everquest) never been defeated by anyone... with the exception of one guild... kind of :/... the GM's got in the way and dropped the server therefore ending the fight before the boss could be killed...so i'm not sure if that counts had the GM's not dropped the server they had a pretty good chance of winning... though having special rules attached to it like the sleeper may only be summoned once per server so im not sure if that would ex him from this being as hes no longer able to be summoned to the game ever again... but hes still an (optional boss) so i figured id throw it out there :)
Mugiwara no Rufi - Cr3\/\/_|\/|@╪3: Kaleo.T.T.C. Kaizoku Ou ni Ore wa Naru!
no one said any Viewtiful Joe bosses, those guys really fit the word "tough". they have tons of attacks and TRUCKLOADS of health, especially on ultra V-Rated, plus, you have to chase them down on battlefields that are pretty large for a 2-d game. it's very anxious watching their multiple-layered health bar go down so slowly... Another Joe and Fire Leo were so annoying.
others i hate:
Sigma from MMX4 - easily the hardest boss from the X series. can't remember his moves today, but he took me 30+ tries, even with sub-tanks and upgrades.
Dr. Wily from Mega Man 7 - i've heard the developers apologized for how hard they made Wily in this one. the primary thing that makes it hard is how large the SNES sprites are >_>
Juppongi from Code of Princess - throws long range projectiles while tons of his henchmen jump you. real fair. its not like Dynasty Warriors either; his henchman are constantly chasing you down and swinging at you, and there can be up to about 8 of them onscreen. what i hate about this the most though, is that before the fight, the game shows a cutscene of all 6 of your party members confronting him, but when the cutscene ends and the fight starts, they're all nowhere to be seen and its just you alone. after enough game overs, it makes you feel outnumbered to the point where its hopeless.
Final boss from Legend of the Mystical Ninja - A giant samurai archer on a white horse that takes up half the screen. he shoots 3 arrows to the sky that fall down on you, and you must get behind one of the arrows as they fall, then jump up and deflect them back onto his face before they hit the floor. what makes this hard is the speed and trajectory of the arrows and his constant left and right movement. i only beat it because of a cheap 2P trick i found out.
Zero.exe from Mega Man Network Transmission - huge sword, fast attacks, collision damage, and teleportation. uses a sword beam attack that covers 2/3 of the screen and does 1/3 of your health. you wont beat him unless you bring Invis chips specifically for that sword beam, and even so, you may run out of Invis and there's still that luck factor where you have to just hope that he doesn't use his sword beam attack again. at least he has some killer boss battle music though :D
Omega from Final Fantasy V - one of those luck-based RPG boss fights. uses insta-kill bombs, lasers that cause poison, missiles that cause confuse, and whirlwinds that permanently remove party members from the fight. this guy just has everything going for him. It really sucks when he suddenly moves 2 or even 3 times in a row, most likely shattering your entire strategy if you came up with one. he's so impossible that there are prophecies and writings in the game telling of how terrifying he is.
thats it from me, pretty fun writing all of that ^-^