System: Dungeons and Dragons v4.X
I'm not saying the Red Box isn't cashing in on nostalgia at all. But, look:
1.) The basic premise of Dungeons and Dragons has always been extremely accessible - explore this cool place, kill the evil bad guys who are in it, find cool things. Now that we have mainstream media accepting the color more readily, it's even more accessible.
2.) It has always been highly recognizable as a game, the way the term is used when we think about board games and strategy games - there is a element of competition, of mastery, of learning a skill set, etc etc Raph Koster ad nauseum. This may not matter to the hardcore rolegamer, but it sure as hell matters to that mom or dad wondering what to get his or her brainy son or daughter for Christmas or a birthday.
3.) Having all the components in one box to provide a single, yet repeatable complete experience makes it aesthetically similar to a board game and allows it to be sold in a lot of the same places. My old Red Box came from a place that primarily sold board games.
4.) As an orthogonal bonus, a self-contained game like that is among the best entry points into the hobby for someone who doesn't know what roleplaying games are. As another bonus, it does not require further interest in other roleplaying games to develop for it to continue to sell.
Accessibility, familiarity, completeness - the Red Box is, and has always been, good product design. There are good reasons to stick with the format that have nothing to do with the nostalgia factor. Just sayin'.