It has been speculated so much that we just take it as fact at this point. But there has not been a solid confirmation that The Lizard is the main villain of The Amazing Spider-Man until right this very second. Actor C. Thomas Howell recently appeared on The Retroradio, and he confirmed that the Lizard will battle Peter Parker, and that his character's son is involved in the choas.
"There is not a whole lot to talk about. Sony wants us to be hush-hush right now. I play a relatively small role. I play a construction worker who's son is caught in the middle of a battle between the Lizard and Spider-Man on the Manhattan bridge. Spider-Man helps me get my son back from this perilous situation. There is some payback there at the end of the movie. Spider-man is kind of hurting. I help him when all of the other people won't. Part of the story is, the nation thinks he might be a bad guy. They don't know what to think. Because of my experience on the bridge with my kid, I know he is a good guy. I pitch in and help out at the end. That is the best way."
To listen to the whole podcast, which is quite funny, CLICK HERE