As I mentioned in another thread, I like the idea of the Lizard being the main focus of Spider-Man 4. I also like the idea of Kraven the Hunter being introduced into the film as the 2nd bad guy. No team-ups this time around. This time Spidey must not only protect the people of New York from the threat of the Lizard, but also his good friend and teacher, Dr. Connors/the Lizard from the psychopathic Lizard-hunting Kraven. I think it'd be nearly impossible to top all of the action we saw in part 3, but I think a storyline involving these two villains could make for some great chase scenes and battle royales.
Things that I do not want to see:
1. Venom's return. Not yet anyway.
2. Carnage. It was way too soon for Venom, the same holds true for Carnage. If pressure from fanboys gets to be too much, save'em for the final flick; thats when Venom could get his second shot; a full-blown symbiote story. Hopefully there would be many films in-between.
3. Love triangles (Peter/MJ/Flash, Peter/MJ/Harry, Peter/MJ/Jameson, Peter/MJ/Gwen, Peter/Gwen/Eddie, Peter/MJ/Harry again). Seen enough of these already. More Spidey vs. the bad guys and happily married Peter & MJ.
Edit: And yeah, I'd prefer the Lizard look something like this as well: