I've never been a fan of genre-mixing, and I doubt the RPG audience and the flight sim audience have much to say to each other.
I've always been keen on genre mixing, if only because I'm kind of a dick. I adored the fact that Mass Effect mixed, with great results, not only because it made RPG fancocks have to play an FPS and made FPS fancocks have to play an RPG, but because maybe at the end of the day both of these groups would realize that they were actually playing a really, really good game behind it all, and that it was so not in spite of but because of this chimeric gameplay.
But moreso than those respectively petty and impossible notions of messing with and enlightening fans, I've always found genre mixes to be fertile, largely untapped space for unique and intriguing gameplay. Now, doing so is tricky, and it requires a lot of skill to make anything not resembling a great big old mess. But these kind of mixes are usually not even attempted except by studios that have a lot of skill and have the best chance of pulling it off, like Bioware with Mass Effect. Other times, they fail, but often with something unique to show for their efforts, like Asobo and Fuel. Did the open-world exploration of a map big enough to fill 35 DVD's and the simplistic offroad racing parts really complement each other that well? Not really, but go ask Shamus Young if it was worth it in the end.
Genres don't necessarily require a full-on, 1:1 mix, either; it often takes only a little of a foreign genre to make the main genre spin in a fresh direction; just ask the multiplayer of any modern FPS game. And in the last console generation, a but of the RPG/flight simulator mix-up Yahtzee suggests had already been done with Ace Combat 5, a game that I love like the flag and which essentially lets you level up your planes into better planes. And I bet a lot of flight sim fans loved that system without even realizing that they were doing the Mach-2 equivalent of level grinding.
Personally, if a big, experienced studio mentioned tomorrow that they were making a full-on blenderized flight sim/RPG Frankenstein monster, I'd shit LEGO bricks- if not for being a longtime fan of both of these genres, then for the chance to bear witness to something that has really never been done before, at least not to the knowledge of myself or the average gamer. Isn't that worth something in and of itself in an industry whose genres are so easily recognized due to how tirelessly reiterative they have proven themselves to be?