I've always wanted to see Peter and MJ's wedding, then it gets interrupted by (insert Spidey villain) and once again Peter Parker must don the suit and save the city.
But the only villains I could see this working for would be: Chameleon and Lizard. Why? Lizard, Connors I feel would keep some his human subconcious before the reptillian side of him took over; that way he could remember people, things, places, etc. maybe his memory leads him to the church, he kidnaps Gwen, and Spidey is too late to save her.
Chameleon he could be hired by an outside source, like the comics, you could have it be The Big Man or Wilson Fisk or whoever, and he starts to follow, observe, and learn everything about Spider-Man and his opposite Peter Parker.