In all seriousness, I think they'll have a lot less difficulty in explaining that this is a reboot than they would have had a decade or so ago. Because of the Star Wars trilogies, a lot of journalists and critics seemed to assume that any movie with new actors playing the same roles was a prequel. Thus Casino Royale was incorrectly described as a prequel to the other Bond movies, Batman Begins as a prequel to the Burton movies and even Smallville as a prequel to the Chris Reeve movies.
However, in light of the movies I mentioned, not to mention Hulk and, to a lesser extent, Punisher, audiences and even critics can now get their head around the idea of a further movie involving a character we've already seen not actuall ybeing within the same continuity of the previous movies.
Admittedly Spider-man has a higher profile than Hulk or Punny and more people saw the 3 Raimi movies than saw the Ang Lee Hulk or Jonathan Hensleigh Punisher; similarly, the gap between Spider-man 3 and the next movie will not be as large as those between Die Another Day & CR or between Batman & Robin and BB. But I think people will cope.