My favorite villain is Taurus Bulba. Most seem to prefer Negaduck, but to me, he's not much different from your everyday cliche cartoon villains except more intense and less comedic. I know, he probably does cliche stuff like wanton large-scale destruction and murder, intricate death traps, and explaining his plans in detail to everyone in earshot because he wants to be the greatest villain/Public Enemy #1, but still... they could have done a lot deeper stuff with such a character and gone in more serious directions.
Taurus Bulba is the villain you can take the most seriously, and I think that's what makes him the best. He doesn't kid around; he wants something, he takes it. Any obstacles, he forms plans for. Anybody in his way, he kills. He got inside Darkwing's head and used his weaknesses against him; Negaduck, being the hero's evil mirror counterpart, was in a prime position to mess with his head, maybe point out how much they seem to have in common, but he never did! When Negaduck threatens to throw a switch to kill several people in a tailorized death machine (done a million times before), it's played for laughs. When Bulba threatens to kill Gosalyn, it's serious, it's chilling, a completely different style:
Darkwing Duck: She never told me any code.
Taurus Bulba: Hmmm, that's a real possibility. But I've always considered myself a gambling man.
Darkwing Duck: No! I'll tell!
Taurus Bulba: No tricks, or she'll make quite an ugly stain on the street.
That exchange alone instantly made me think this guy was one of the best cartoon villains I ever saw. It's a shame that they only brought him back to say he would be back and then... he never came back. Except to cause Darkwing one episode full of more fear and emotional turmoil than I ever saw, certainly moreso than whenever he's fought Negaduck.