Some days ago I while searching for Spiderman 4 on the web I just found a video interview of Stan Lee, the creator of Spider-Man.
The interview dates back to one year ago. But I think it still sounds right and it would confirm the Lizard hypothesis:
Stan Lee Talks Spider-Man 4.
So Stan Lee asserted that:
I think unlikely that any producer or scriptwriter would counter Stan Lee's viewpoint.
So it's almost a given that the Lizard will be in Spiderman 4. Maybe the Lizard will join forces with some other villains to fight against the superhero Spiderman though.
Update as of 2009/03/16:
"We’re definitely talking about working from all the material in the comic books and nothing [invented] outside of that, 'Raimi continued. 'All the characters or villain or villains, whatever we decide to do will be from Stan Lee’s creations or those that came after him."
Sam Raimi
So Sam Raimi will stay faithful to the original source material. And I bet he will listen to Stan Lee: the old man is still the old man in the house! Quite sure we will have the Lizard by now!
;-)