The shape of the next "big thing" in gaming depends on whether you are considering existing gamers or the larger public. The next "big thing" for the existing gamer population is likely to be some kind of smart phone app that functions as a combination automated character sheet, random number generator, probability calculator (so you know if you should try a certain move, etc.) and rules reference.
As for something that will break big with a non-gamer population, a la Vampire in the 90's, that's a different story. IMHO the game that will draw current non-gamers into gaming will certainly NOT be D&D or anything like it. In fact, for any non-computer RPG to have any success in the wider world it will have to be completely disassociated from D&D. Likely, it will not employ number-based traits, or much math at all. It will be based on an interactive story model, and may rotate the role of story presenter. It will certainly not feature "kewl powerz", a focus on combat, or any features that computer games frankly do better. It will be something of an excuse for face-face socialization in a world that is becoming more depersonalized every day, although it will also be easily playable through social networking sites. It may very well be the sort of game that existing gamers will hate, and not consider a "game" at all. It's players will certainly not see any connection between their pastime and "D&D" or its players.