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
Nightmare Reaper plasma robot guys and Kenshi's holy nation