It might be better to fly into an eastern city and drive an eastern loop for a week and a half. Return the car to the same airport. Then fly to a western city and do a western loop for a week and a half. I think the flight costs would probably be less than the one way drop off costs. And, unless you are interested in long boring drives, there's no reason to go east of New Mexico or the Front Range of the Rockies, or west of the Appalachians.
Or, if you are really interested in looking at miles of cornfields, do 3 cities with 3 loops--NY, Chicago and San Francisco.