As much as I want it to be Diddy Kong Racing Returns, I really think it would be immensely beneficial for Nintendo to let them be their Naughty Dog and have them produce a new AAA mainstream appealing western IP.
Like I said, Retros effort with Metroid and Donkey Kong absolutely outclass pre-Uncharted ND's efforts with Jak & Daxter or Crash. With that in mind, there is so much potential in what Retro could do when ushered in a similar direction at Nintendo, and it would give the company a seriously needed exclusive IP that would appeal to an audience they are severely lacking and desperately need and have neglected for generations.
So my real hopes are on that. A big, new IP from Retro. One that appeals to the type of person who thinks that Uncharted 2 and TLOU are the greatest games of all time. Only made by Retro, who are frankly much better game designers than ND, meaning this potential franchise could be that much better than those, at least from a gameplay and level design perspective. Then all they'd need to do is hire a decent writer and VERY good VA talent. Retro could seriously make something outstanding.
Launch that game with the NX/make it a launch window game, and that would be titanic for that system, especially when it comes to making 3rd party western games successful on the platform, which is the biggest reason they need to do this.
EDIT: I don't even think it needs to be Rated M. It might actually be a more successful franchise if its Rated T. I always compare Nintendo to Disney - this could be their Pirates of the Carribean. It just really needs good production values, especially in the script and VA where Retro's games traditionally lack any. I think they can get the presentation, I know they can nail the music and sound design, and the gameplay will be unrivaled by those of its ilk. It's the storytelling that would make or break its appeal, and they'd need to really take that seriously.
