Something like a Gran Tourismo or Forza
Those titles themselves aren't going to happen.
Gran Turismo is a Sony franchise.
Forza Motorsports is a Microsoft franchise.
But I do believe we need a Nintendo franchise to rival them. And not something like F-Zero. That's great, but it's fantasy driven. Nintendo shouldn't be too upset if they can develop a really good motorsports/rally simulator, that did very good competition to those titles. It doesn't have to be racing car based either. They could probably throw in ATVs and motorbikes. In fact, they could give it that Nintendo feel by having multiple different vehicle types race against each other simultaneously.
I know that Nintendo has Wave Race, F-Zero and Mario Kart (which I'd prefer to have bikes from now on, Luigi's Mach Bike for the win!), but a Nintendo branded realistic game wouldn't hurt. And it doesn't have to be racing, anything really.