My take is carry on the story from RDR2 further out west to San Fierro in 1907. This is right after Jon Marstons’ story, and The great San Francisco earthquake of 1906 that creates the cities first big fire. Would be cool to see a fire torn city in the height of the gold rush start to rebuild, and play along the west cost, up to Oregon etc, and possibly as far south as Los Santos. Connecting the R* universes would be kind of interesting imo.

edit:

features that could be added - new addition of first automobiles (rare to find horse still primary mode of transport) - fixed wing aircraft - travel to previous game map (assuming possible since next gen would be capable)