Unless there is something in that first 1,500-2,000 miles you really want to see, I would consider flying. And flying into one city, rent a car one way, and fly out of another city to avoid having to return to the original airport. Not to mention the 10-15 long travel days going and coming from home.
A number of years ago we flew into Salt Lake City, rented a car, toured SLC, drove up to Jackson, WY, Grand Tetons, Yellowstone, Cody, Little Bighorn battlefield, Devil's tower, Deadwood, Mount Rushmore, Crazy Horse monument, down to Cheyenne, and flew back home out of Denver. You could add in as many additional places as you wanted. One way car rental from one major city to another was very little price difference. And air should not take any more FF miles either. Did a similar trip from San Francisco up the coast to Seattle. And another from Savannah to Nashville. I love the RV, but sometimes flying is the better option, at least to us. On those particularly far from home trips, if some emergency arose at home we would be hours from home, not days.