Word is coming from Sony that Sam Raimi and Tobey Maguire will be returning for Spiderman 4 & 5. With a release date for Spidey 4 to be in 2011. No word if Dunst will return but I think it'll be unlikely.
As for the villain, its been said that once the villain has been named, we will know instantly who is playing the villain. Which pretty much 100% locks in Lizard as the next villain since Dr. Curtis Connors, played by Dylan Baker, was in Spiderman 2 and 3.
Stay tuned for more as this comes along.
Also, this may or may not totally throw the 167th rumored Evil Dead 4 plans in the trashcan.