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
DS2 DLC bosses aren't fucking around lol. Fume Knight is an amazing fight. Maybe the hardest, but its a really satisfying boss fight. I hated the the Queen in the Sunken Crown. Way more annoying fight for me personally, and not even satisfying to win, just glad its over. The Dragon fight after that is rad, him and the Fume knight are my favorite