I think that they set up both the Lizard and Man-Wolf in the last two films. They introduced both Dr. Conners (Lizard) and John Jameson (Man-Wolf) in the Spider-man 2.
In Spider-Man 2, John Jameson is Mary Jane Watson's fiance. Mary Jane later realized that she did not truly love John and left him at the altar for Peter Parker. The movie includes multiple references to the comic book story arc where John Jameson becomes Man-Wolf. Jameson wears the same medallion that in the comics turned him into Man-Wolf, and he is portrayed next to a full moon in another scene.
So, it might be that Spider-man 4 will have super-human animal motif villains and heros like Man-Wolf, Lizard, The Scorpion, and of course Spider-man. There are other villains they could bring in as well. What I liked about Spider-man 3 was how they brought so many super-powered characters into one film and made it work so well.
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