Bear with me. I would love to see the next game take place in a post-WWI image of a Chicago-esque city and the surrounding country. This is the golden age of crime in America. As a protagonist, the game could follow Jack Marston (though this would only be an indirect sequel to RDR) as he returns from WWI. It should take place over a fairly wide set of history, through the twenties and thirties.
This would give R* such thematic boons as prohibition, the great depression, advancing technology, (on a perhaps more serious note) the looming shadow of the second war and the holocaust etc. The widening class gap between poor and rich especially could provide commentary on today's America.
In terms of story, I say apply Vs heist model to the golden age of bank robbery, and even go so far as to heavily base Jack's play style and story on John Dillinger. We could follow him from returning home to getting swept up in crime, perhaps involved with old comrades from the war. He could be allied to and at odds with the mafia and criminal underworld in various ways in addition to an often corrupt law enforcement establishment, in true R* style. His missions could involve working as a low level enforcer for a local crime lord in his home town, being involved with illegal alcohol sale and production and gang violence, moving up steadily to work with higher ranking gangsters, making connections old and new, building a gang to take on increasingly advanced robberies of banks, trains, etc. There could be all sorts of great characters thrown back to history taking inspiration from Al Capone, Baby Face Nelson, Bonny and Clyde. The player could even do battle with the KKK and other bizarrities like that.
In terms of gameplay, I think multiple protagonists might work well, but added on top of the primary one who leads the crew. I kind of picture Jack as the savvy criminal, but there could be a slightly older, somewhat mentor like bank robber who's been in prison etc. Perhaps he reminds Jack of John. Perhaps a friend Jack made while in the military who's reliable but also suffering from shell shock. There could be a female character on the run from the life of an oppressed woman in an era of women's liberation
Anyway, you've got room now for cars and horses in the same game, some planes, early tanks. Obviously no sports-cars in the traditional sense, but the Dillinger-era bank robbers used supped up cars as a means of evading police, so there's room for car improvement and fast vehicles.
You've got a wide array of weaponry including all the staples like the 1911 pistol and the Tommy gun.
You've got all the cool fashion of the era, the style, wealth and decadence. I know R* could just nail all of that, the glitz and shimmer covering up the ugly realities of the day.
Lastly, there's a HUGE array of great movies to set the tone from Gatsby to Public Enemies, not to even mention countless great black and whites.
Anyway, there's my idea, sound off with your own.