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
Sirus from Path of Exile. What an awfully designed boss, 90% of the time you can't see shit because of the fart clouds he spawns on the ground. I barely killed him this league after what, TWO YEARS of trying him on and off. Doubt I will even go for him in the next league or any other in the future.