A boss you died to 1000 times, an enemy that still strikes fear into your heart every time you replay your favorite game, etc.
For me it's the Blood Starved Beast from Bloodborne. I died to it probably over 100 times my first playthrough no matter how many times I replay the game I still get torn to shreds repeatedly. Honorable mention cazadors from New Vegas
Wiegraf in Final Fantasy Tactics, favorite game of all time then it throws this wall at you mid game you're most likely not prepared or leveled for, solo.
God I remember this fight softlocking me the first time I got there. This fight singlehandedly traumatized me into keeping at least three files of every game I play
I gave up on my first play through back on release. It wasn't until like 5 or 6 years later I came back to the game lol
I ended up selling my copy to a friend because of this fight.
Damn Square for making this fight so hard, truly a masterpiece of a game otherwise.