There's a couple things in particular I'd like to see change if they do make a sequel.
For one, if they do an honor/dishonor system again I want there to be an actual point to playing dishonorable this time. In Red Dead Redemption there was zero point in playing a dishonorable character, it just made the game much more of a hassle than it is playing as an honorable character, many missions default to giving honor just for completing them and don't have a real dishonorable option, monetarily there wasn't much if any cash that one could get by being dishonorable over simply being honorable, and the basic plot and ending don't change AT ALL if you're dishonorable instead of being honorable. It just makes the very existence of the entire system seem completely frivolous. There also should be great rewards for the player that acts like a scumbag in addition to great rewards for the player that acts like a great guy/gal (female protagonist options should be in there too BTW) and bad things should happen to players that act like a scumbag and bad things that happen to a player that acts like a great guy/gal, in roughly equal proportion. Making choices matter requires there to be bad and good results for making those choices, but always at least one of each in everything.
For another, I want these stranger missions to end better, not to mention the rest of the missions. Most of RDRs missions just end up being horrific with no good or even just middling conclusion with everybody involved except the player themselves either being scumbags, insane, or both, and while it's fine for that to be true sometimes regardless and make us feel depressed there should be plenty that end well regardless and give us warm fuzzy feelings, just to balance the former out. Also, if there are choices presented I hope that this time that there's at least one that has the missions end well if you take them, rather than with most of RDR's missions that as mentioned ended badly regardless of your choice. What I always hate most in any game that tries to give you missions with choices is when they then never have it end well no matter what you choose to do, worst of all if it you're railroaded into ensuring that it doesn't end well just by doing anything. One for RDR that comes to mind is the Bigfoot mission, which the only way you can have anything good happen is by not playing the mission period, and any game that gives choices for it's missions should NEVER have the only good choice not doing the mission at all.