Honestly, while I was learning Python for quite a while, I ended up canning it due to it not feeling like 'The Highway'. While I'm totally on-board for The Highway to become a series of varying games, I'm not sure I'd want it to be a rougelike or necessarily open world. Fuck I'm not sure I'd even want a main focus on survival or road trips.
With the overabundance of survival and 'realistic' games on the market I'd think I'd pull a Hotline Miami and move to game maker. Figure out what kinda art I'd use (not pixel art, I'm getting sick of that shit), most likely something that crosses the lines between PS1 graphics (very blocky or 'polygonal' charaters) with some cell-shading to give it some comic book feel. Hell, I think The Highway might make for a great isometric game with 'semi-open world' areas.
You start on the main map and choose from three starting cities. The Flooded New York, the chain of island-buildings in Miami/Georgia, or in the middle of DC where you'd start with a boat. And from there you choose different points on a map to head to, similarly to Oregon Trail or Organ Trail. It calculates what happens, food gets deducted, etc... etc...
But when you arrive at the "city" or "location", it opens up similarly to the new Shadowrun game. You take your crew out of the RV and explore the surrounding area, finding quests, uncovering various secrets, finding special merchants that carry things at both discount and rare items. Making it feel more like Fallout 1&2, with you running around these small sections of compact content that branches off to more open areas.
Example: You head into Detroit, you all pile out of your filthy RV and make way towards the nearest settlement that is just up ahead. They have walls set up around several buildings. You got a quest back in New York from Rose's Raiders to destroy this place. So you plant some explosives right near the entrance (and I'd even include simplistic destruction mechanics) and blow out the wall. Combat then ensues similarly to the old Fallout games with a tad more futuristic things. And if you make it out of the situation alive, you can loot the area return to your RV.
Then you can: A. Take a long trip back to New York and turn in the quest. Or B. Take the loot and run.
Actually the more I think about it, I honestly think this would be the best approach for The Highway: The Game. You get to explore all the USA, in what matters. Blips would appear all over the map and you drive your RV to them. And when you reach that particular 'blip' the game sheds its 'semi-Organ Trail' facade and becomes a full CRPG, letting players choose which settlement or piece of wilderness in the city to explore.
Then if you do certain questlines it'd unlock more locations to explore (like a secret military base).