Welcome aboard the RoadTrip America Forums!

Well, you do have to cross the Appalachians, and roads in general are designed and built to connect rather than avoid population centers. Still it is possible to design a route that will seem like what you've asked for. Remember that Interstate highways are built to design criteria which limit the steepness of any grade and the sharpness of any curve, so other than the scenery you really shouldn't feel as though you're driving through mountains. The worst part of your trip as far as congestion goes is the initial leg in North Carolina, and familiarity with parts of it should ease the burden. You just head west on I-40 through Greensboro to Winston-Salem where you switch over to US-52 up to join I-77 just west of Mount Airy. I-77 up to Charleston id probably the most mountainous portion of your drive, particularly the West Virginia Turnpike, but again it's excellent quality road, and if you just enjoy the beauty you should have a great time. At Charleston, hop on I-64 and take that the rest of the way to St. Louis. After you leave North Carolina, the only sizeable cities you'll hit are Charleston, Lexington and Louisville. not bad for a trip this long. You'll need two days for the drive and halfway would be roughly Huntington, WV.

AZBuck