Ornstein and Smough from Dark Souls. The series have plenty of difficult boss fights but this one is earlier than most and the biggest difficulty spike in the entire game IMHO.

Outside of the Souls games, there’s Lil’ Hunter from Nuclear Throne. I tried to beat this little trashcan SO many times and succeeded only once. It’s insane.

Also shout-out to Hush from the Binding of Isaac for almost giving me a heart attack when I was fighting it as the tainted lost. Never again.