Worst: Hackman's Lex Luthor. I said it. He was/is a capable actor, but that Luthor sucked.
Batman Forever's Two-Face, again, Tommy Lee Jones, capable actor, but the take on the character was wretched.
Both were great, and both had their downsides...Nicholson's ties to Batman's past and Ledger's seeming infallibility/great luck. But both set the bar for onscreen comic book baddies.