The birth of the Wild West didn't necessarily take affect until the mid-late 1870's. That would be very interesting! Some people have suggested that it take place during the prohibition era (which would just make it another GTA, so it's probably a no-go). I think the next Red Dead should be the last one. What, really, is there more to say after the next one?
Yeah a prohibition era game would be too similar to GTA! I would love to see a prequel story about the life of Uncle and what led him to the state he is in at the time of Red Dead Redemption. I thought he was an interesting character for sure! There was a lot of questions about his story and how people treated him. But you're right, if they chose a new storyline, they'd soon run out of options to say any more!
I always got the impression that John Marston was too harsh on him! Maybe I need to replay it, it's been a couple years!
To be honest I'd prefer another Red Dead completely unrelated to Redemption. A fresh start.