Any enemy that explodes if you don't kill it in time. Looking at you Final Fantasy.
The final boss of Persona 3 FES, you get it down to a sliver of health and it does an attack that gives multiple party members status ailments. The fight takes about an hour. I quit after 2-3 tries.
TO THIS DAY I've never beaten that game. Boss gave me the kind of quiet anger that makes you just stare the screen. So much time investment for that BS desperation attack.
Any boss that's so resilient it makes me yell out "JUST GO AHEAD AND DIE!"