The clone saga could work, it would just need a hell of a lot of adjustments. Here are some changes I would do:
Have it be Spider-Man 6
*Base it on the first clone story (ASM 149-150) and Revelations.
*Just one plain Spider-Man clone (maybe later on his costume changes so its better to identify whos who, but dont change his name or anything like that).
*No Kain, no Spider-Cide, no Gwen Stacy clones, no multitudes of other clones; just the one clone.
*No Jackle
*Like the comics Green Goblin is behind it all, though I would have it be revealed early on in the movie. The movie is the last one and would have to have a big villain leading it. Though I would have liked to seen Doc Ock return, most people would accept Norman returning more than Doc Ock (mostly because Norman is Spidey's #1 foe and Ock's redemption in SM2).