This quote: â€œWhat sets the Spider-Man villains apart is the complexity of their relationships with Peter Parker. Rhysâ€™ incredible ability to embody both warmth and rage makes him the ideal choice for this characterâ€ suggests that the villain will have some personal connection to Peter.
At first blush, that rules out villains like Vulture and Electro. But then, Sandman didn't have a Parker connection in the comics either, but his origin was tweaked for SM3.
So I guess I'm saying I have no idea who the villain will be. (Ok, I guess the "warmth" bit rules out Carnage. And I'm pretty sure they're saving the Hypno Hustler for the sequel, Spider-Man 2: Electric Boogaloo)