There aren't many villians left in Spidey's rogue's gallery who are well known, and who I think could have an interesting plot developed around them. The Lizard is certainly the top of the list for me. Dr. Connors relationship with Peter, and the fact that he has a family could be used to create an interesting dynamic between Spidey and The Lizard. I would imagine a side story about Kraven could also be worked in. I hope they stay away from guys like the Shocker or Scorpion though. If not, they'd better engineer some better backstory for them. Normally I don't like the movies to stray too far from the essence of the character, but some of Spidey's classic villians just aren't that interesting, and haven't held up well after 40 years.