I personally want Tobey to do 1 more in SM4 for a number of reasons (get Raimi to handle Lizard properly and finish off the Peter/MJ will they/won't they with a marriage between Maguire and Dunst and not LaBeouff/Mandy Moore or whoever). But after 4, I think they'll have said their peace on the characters and will be getting kind of old so after that, I'll be more open for a new Parker.
As for Franco. Nah. I think Maguire is a much better actor. He was certainly a better actor back in 2001 and 2002 and while Franco was impressive as Harry in SM3, it was the first time he was really impressive since the James Dean miniseries he did back before Spider-Man. His leading roles in Anapolis and Tristan and Isolde were stoned and boring. He was passable in the first two Spideys. Maguire has always been a very good actor and nailed early Parker in the first two. I think he is growing into Conway's Parker in SM3 and doing well with it, too.
Now in retrospect, Topher Grace WOULD HAVE BEEN REALLY INTERESTING. But I'm not losing sleep over it and think Maguire is fine for Raimi's vision and they have a good rapport. So why bother worrying, then?