I'd try and adhere to a theme like Raimi did. The obvious way to follow revenge/forgiveness would to be extend that to acceptance and redemption. Pair Peter up with Dr. Connors, and have them bond over their strained relations at home. Connors is struggling in his marriage, and becomes obsessed with regrowing his arm as a means to fix his life.
Peter sees his future self in his mentor, and worries that he too is doomed in love. Him and MJ are stable, but attending couples' councelling to repair the damage caused in the last film. While Mary Jane appears to be pretty content, Peter can't shake his fears and is looking for a big fix of his own.
Connors' experiments fail, and -shock twist- turns him into a giant lizard. Kraven the Hunter, a TV game hunter, is in town and vows to hunt the creature. He is charismatic and ruthless. Spider-Man finds himself caught between protecting the city and the beast that threatens it, all while Kraven's public exploits begin to shake the trust in our hero.
Throughout the film we see Peter struggle to accept his past mistakes and move on. This would be reflected in Dr. Connors' dangerous attempts to "fix" his life, and mirrored by Kraven, a man who views life with reckless abandon. Spider-Man will eventually regain his trust in himself and the city, personalised by Dewolf, a skeptical cop who will be swayed by the events of the film.
