If we're talking Transformers, the worst of the worst is either Galvatron, who obliterated the [all but a handful] entire population of Earth and decimated nearly the entire ranks of the Autobots. Only leaving Rodimus decaying body holding, ironically, the Twin Towers up as a monument to the futility of the Autobot/surviving human cause. Or perhaps Starscream, who basically nuked all of San Francisco from the War World. Bludgeon could certainly get props for attacking the defenseless planet of care bear-like aliens on Klo...then using said planet as a death trap for Autobots.
If we're simply going on severity of action, Thanos certainly reigns supreme since he tried unmaking reality more than a few times and killed earth's mightiest warriors at least once, before having the event retconned.
The Joker certainly has more than his fair share of grizzly and perverted murders including but not limited to the paralysis of Barbara Gordon and the "death" of Jason Todd. I think he ever released this virus foreshadowed in "Batman R.I.P" I'd be forced to move him into the top spot, that was disgusting.
I'd have to give Mr. Sinister major recognition as a villain. He pretty much owns the art of ruining people's lives, specifically through subtle and manipulative means. Starting with making Scott Summer's childhood a living hell and moving onto turning Gambit into an accomplish in a huge mutant mass murdering spree. That has to count for something.
Then of course there is the Nazi War criminal, Red Skull. I met a holocaust survivor today as a matter of fact, and I have to say that was a grim reminder of an event so horrifying even the mind of a comic creator can barely think of anything worse.