Please do NOT take to the comments and tell me it is Ghosts and Goblins, because it is not. I am speaking of Loki, from the GENESIS version, Ghouls and Ghosts. Now, before any of you leap on me and rip off my arms only to beat me with them, let me explain why he is on this list. It really is a two-fold thought process.
One, because of the grueling challenge it took to actually get to him. Ghouls and Ghosts, much like Ghosts and Goblins, was an unforgivably difficult game that derived MUCH joy from torturing the player, so to make it to Loki without a broken controller was a remarkable feat in itself.
Second, and what really drove the whole battle home for me was that fact that he was freaking huge and pretty scary, too. I was facing the Devil, and to me, it LOOKED like the Devil. Granted, the actual boss fight is sort of weak when you look at it now (why would he not just actually stand up to crush you?), but when I was just a wee lad, Loki was the first time I really understood how scope could factor into an awesome boss fight.
Also, the Devil had no dick, which I found even more unsettling. But honestly, how odd would it have been to see two, dangling red balls just above Arthur’s head? I think they made the right choice there.