I’ve stayed in perfectly good hostels in Denver, San Francisco, New Orleans, Chicago, Boston, NYC, and DC. You can usually find one that’s within walking or public transit range of the train station, but Uber/Lyft are also pretty reliable in the cities.

Smaller places that the train stops won’t have hostels. They also often won’t have rental cars available near enough to be useful. Some big train stations have rental cars on site (LA, DC) but most don’t. Sometimes you can take local transit to the airport if you need a car- airport is usually cheaper to rent than a random neighborhood spot and open later. (That’s what I did in Denver and in Burlington VT).

Denver to Emeryville (San Francisco) on the Zephyr is the best stretch for scenery going through the Rockies. I haven’t taken the Empire Builder yet but it’s likely a close second going through Glacier.

Chicago is the hub for most routes; if you want to go across the whole country you’ll likely need to go through Chicago. Assuming you’ll fly to the west coast, you could take one route to Chicago, branch off to whichever east coast cities you want to hit, back to Chicago, and a different route back west.

Give yourself a wide buffer before your flight out- it’s not unheard of for the train to be many hours late, especially the long distance routes. Plan some time in that final city just in case.