Phantom Miria
Queen of Feuds
Because this is relative, I say Nozdormu.
Ultimecia only has one real destructive feat of significance, which she required a set amount of factors to pull of and she failed.
Dark Khan merged two realities together, some perished in the process and the universes melted together, but that is also a feat of limited destructive powers, since it was not destruction by choice but rather at random. Nothing imply that he intended for anyone to perish, which in itself imply that he has no control over his most destructive feat other than the concept at whole.
Pyron is a physical powerhouse. He absorb planets and slap them around, but thinking relative, Pyron accomplish the things he do through brawn and sheer size. He has a few other tricks up his sleeve, like his created minions and energy manipulation, but again, mostly brawn. Things could be a lot worse. All things considered, Pyron is not all that destructive in a relative comparison to other characters.
Nemesis? If this is Resident Evil Nemesis, I will just go ahead and stop right there. If it is not, I have no idea who this is.
Why do I say Nozdormu? This is a character that has shown the capability to grasp all of reality, a character who can distort and destroy time and space. Destroying something is one thing, but utterly shattering something into its very fabric of existance, to the point where it cease to have ever been: He has my vote.
Sure, Ultimecia had a neat trick, but she failed to pull it through and she had to drain a number of magicians to reach the point where she had the capability, something that in the world of fiction is named plot devices.