1.) Andrew Garfield will be too much like his character from Social Network.
2.) Terrifying Hollywood influences will unite to corrupt and "Tweenify" the film.
As far as number one, well Toby Maguire was so natural as Spider-Man he pretty much defined the role (like Christopher Reeves did for Superman back in the day). Maguire was able to be nerdy and charming, soft spoken but heroic, and always a beat off perfectly. Will Garfield be able to do the same? I'm not saying he has to "be" the same character as Maguire. No not at all. But where as Maguire was able to be the character pretty easily because he was already so much like the mythic Peter Parker that he didn't have to stretch to many acting bones (at least in terms being the character), as far as I can tell, Garfield is a bit more presumptuous than the humble and goofy comic book hero. Maybe he can make the leap, and surprise us all with a great character performance, but if he just plays "Garfield playing Peter Parker," I don't think it's gona cut it (remembering him in Lions for Lambs, he was on the too-cool-for-school side in that as well, which gives me little hope for his ability to act outside that range).
Number two is about the anime-ification of certain marvel heroes to give them a more "pretty boy" appeal, but most my fears regarding what a studio might do post-Twilight. If that's what Hollywood decides to sell, some oversexed, operatic melodrama with the ipod from the nearest H&M on shuffle in the background, even a great performance from Garfield won't be able to save the all too soon reboot.