Definitely the four boss hellhole you have to pass in Cave Story. I consider them all one boss since you can not save in between them.
If you've never played Cave Story...
..it's a platforming bullet hell/shoot em' up (Like Metroid but WAAAY harder.) about these bunny people called Mimiga that are being threatened by the main antagonist, the Doctor (No, not the timelord. Sorry Doctor Who fans.). He wants to use these red coloured flowers as a steroid on the Mimiga so he can use them in the ranks of his army. A lot to take in, isn't it?
I've still yet to beat them, unfortunately. I'm not the best at video games, but I still love them! <:^D
I guess it would be from undertale.Undyne the undying and sans
Also from the game i am currently playing >.> the binding of isaac Mega Satan
Hmm - Hardest bosses?
I would says Sans but... He was a chump.
I otherwise can't think of any bosses that were exceedingly 'hard' as such, more annoying than anything. That said I'd have to go with the final boss of Rainbow Six: Vegas 2 - that damned attack helicopter when you (and potentially your co-op partner) are stuck in a tennis court.
That fight sucked, especially on Professional mode where the slightest breeze from the explosive rockets it fired sent you hurtling back to the start of the fight. >.>
Wait till you get to the final boss, It's insane. I originally started on the portable version but then after i beat that one i tried it out on ps2 for the FES ending, which is worth watching on youtube if you dont have a ps2 to play it. Or if you just dont have the patience. And after all that theres these little challenge bosses that will murder you.
Thanks for the heads up! I bought the FES version years ago, but it got scratched to oblivion :(
I would love to try it out again sometime though even with the gameplay being more difficult since you can't directly control party members.
Thought of another boss that's difficult, but mostly because there's so many bugs in the instance it's hard to get through it! Mordremoth in the Heart of Thorns Expansion for Guild wars 2
Holy cow it took me 3 or 4 attempts that each took up to half an hour because of the mini-bosses before it that you can't skip. Then you have to hope nothing breaks during your actual fight with him where plenty can go wrong. It's a bummer too because the encounter is actually pretty enjoyable and cool, but the glitches and bugs totally ruin it :(