As per Development Hell.com:
a source close to the production of Spider-Man 3 confirmed for me that the main villain played by Mr. Thomas Hayden Church will in fact be the Chameleon.
Church plays Dmitri Smerdyakov, who goes by false name Dr. Turner at Peter's college. The Chameleon also has a brother in this film, which will set up Kraven the Hunter for a future sequel I'm told. Le'ts just say that the Chameleon will use his powers of performance and identify theft to bridge a gap between MJ and Peter Parker in this film.
The producers and Raimi have a big publicity event right before production starts to make this announcement. Look for it after Thanksgiving, with production to start this winter. This will begin the hype for Spider-Man again. They will also start issuing a new animated DVD featuring the Chameleon right before the new movie hits theatres.
Also, Harry does become the Second Green Goblin, but only at the very end. He's kind of like Anakin in Episode III -- growing evil throughout the film, and not donning the full mantle of recognizable villain until the climax.
It's official: the Chameleon is the character Hayden Church will play, I promise.
This comes from a VERY reliable source, so we’re saying you can take this to the bank!
Still no word on Topher Grace's character though.....hmm.......Venom? Sandman? Vulture?