A returning character?
Just as they did with the two previous games, which were very close in story and cast, you can imagine a side character stepping into the lead role in RDR3. Rob Wiethoff, the actor behind John, and Alex McKenna, the actress behind Sadie Adler, have both said in press conferences that they would be delighted to reprise their roles for a third installment.
Sadie Adler as the main character of RDR3 would be a real turning point in Rockstar's history, since they have not yet created a female lead. It might also ease the old controversy around the fact that women could be hit and killed in GTA 5, a controversy that faded quickly because it makes no sense to be able to kill men but not women in the game. These days, though, it is entirely possible that a new debate around the issue could flare up. You could also argue Rockstar hasn't done it yet because their fanbase is mostly male, and some of them might not identify with a female lead.
You could also picture Dutch as the lead, since he is one of the oldest characters of interest appearing in Red Dead Redemption. Remember that the first RDR took place at the very end of the Old West (1911), so a direct sequel is very unlikely because it would no longer be a western. A game set in Dutch's younger years would be possible but perhaps disappointing, since he is ultimately the villain of the story, and many players would not enjoy the idea of playing as him.
It is all pure speculation, and one of the most likely outcomes is that we take a leap into the past with brand-new characters, sending us back to the 19th century. Why not during the Civil War, like The Good, the Bad and the Ugly?