Maybe "Peter's gone" as in "I am the spider"...
Peter dies and then gets replaced by a real spider bitten by a radioactive human.
Your idea could be done easilly with another character, but having another "death of spider-man" story line right now would be lame
Nope. There's going to be a mini called War Scars and it'll feature an unheard of black guy who'll turn out to be Peter Parker's son. He'll be taking over as Spidey from Peter as Peter retires permanently.
Well, Peter Parker said he couldn't be Spider-Man if he killed someone. The "No one dies" mantra Peter has been living by since the beginning of Big Time will inevitably bite him back very soon, somebody will either die on his watch again or he will more likely be forced to kill to save more. It will certainly be interesting to see where the No one dies idea climaxes.
I wouldn't mind someone else taking the mantle of Spider-Man as long as Peter and Mary Jane end up back together and were still part of the book as members of the supporting cast.
And I definitely wouldn't have minded if Ben Reilly had kept the mantle when Marvel pulled their switch as long as Peter and Mary Jane were still in the book with him as supporting cast members.