Having May die as a repercussion of Peter's actions before Peter could tell her would really tear Peter away from 616. It would be horribly sad, and I kind of hope it doesn't happen for Peter's sake, but NO ONE can deny that it would have ten times the punch of Gwen's death.
Have you ever wondered what could drive peter to Kill? and what would the military do then? SHIELD would hunt Spiderman down. Fury would want Spidey locked in a cage and tested on until they can reproduce the experiment on a person who can control their emotions.
He wouldn't be able to hide anywhere except maybe the X-Mansion, and do you think Xavier would harbor a wanted criminal on the whims of a 15 year old girl? Do you think that Kitty's mom would be able to hide him from the most powerful Military organization in the Ultimate Universe?
There is a hit out on Spider-Man, and these people are smarter than Peter on an espionage level. They are going to find out who he is and where he is, and then May is going to get hurt.
With Sable, Deadpool, SHIELD, Roxxon, AND Fisk all breathing down his neck, there has GOT to be some fall out.
Personally, I think that would give the book the dynamic it needs.
Peter also should have a relationship with Reed Richards... I mean, they are close in age, and Peter would be enthralled by Richards' mind, and the capabilities of his facilities...