I had this conversation with Nirolak, about what Retro could make that would attract a strong Western audience, and we did come to somewhat of a conclusion that Metroid Prime is pretty much that. It just came about at the wrong time, and skimped on a few presentation choices.
Something like BioShock is an excellent example of a non-Gears/Call of Duty game that appeals very strongly to the mass market. It's a game that hooked many new gamers this generation. If you look at how Prime operates, they're alarmingly similar. The use similar concepts and similar thematics to draw the player into the experience. Only Prime came about last generation, and on a system struggling to sell in the West. A lot of what made BioShock so appealing (excellent graphical presentation, audio recording, proper dual analogue controls, etc) wasn't available.
Whereas now it is. Funnily enough, a Wii U Metroid Prime similarly paced to the other Prime games, with production values to match modern titles, could do a pretty good job of hooking your typical Western gamer, without losing credibility or core formula. Even on a thematical level, Prime and Metroid in general stems close enough to 'grown up' than 'kids' without being obnoxious about it. Metroid can be quite scary, tense and mysterious while still be Metroid, and these kinds of things will appeal to older gamers.
In a hypothetical alternate universe where the Metroid Prime series never happened, if the Wii U was shown off with the Metroid Prime we know, only with modern graphical presentation and control standards, Nintendo would probably earn a lot of positive attention.