I would like to see the game set earlier in the period, perhaps setting the game around or during the American Civil War.
Also, despite all the fans of the period and regular westerns, I would like to see a somewhat wierder plot. Bring in more, and more overt supernatural elements and such (they were present in this game, but not a major focus).
One "problem" I had with RDR was that it was very stereotypical, it could get away with this because it's pretty much the only game of it's type. I think that if they did another straight "Western", they would wind up recycling the cliques and to do it again it would become almost painful.
I also think the civil war era has potential as you could act as a mercenary and play both sides. It also gives a lot of space for political incorrectness (which I think we need more of). For example I was a bit disappointed that I couldn't be the quintessential "Indian Fighter" in this game. I don't know why, but when the game came out I had visions of being able to head out to villages, scalp natives, and turn them in for a bounty.
Don't get the wrong impression about that, I've worked for two differant tribes, I have nothing against Indians IRL, it's just part of the romance/excitement of the period, and despite being morally bankrupt by today's standards, I don't feel it goes any further than what you see in crime games and such.