Back in October, director Sam Raimi hinted that one of the next villains to face down Peter Parker in Spider-Man 4 might be Dr. Curt Connors, AKA "The Lizard." In response to an MTV fan poll that picked The Lizard, Raimi said:
I love the Lizard. There's a great story there in the Marvel comic books about Dr. Connors.
While Raimi's comments may not be an indication that The Lizard will feature prominently in Spider-Man 4, recent comments Tobey Maguire has made to MTV lend more weight to that possibility.
I'm more familiar with Lizard and Mysterio, and I don't know — I like them as villains. I think they're great, and Lizard obviously has a really personal relationship with Peter Parker, so we often will go towards that kind of stuff.
Production on Spider-Man 4 is slated to begin in March.