We are planning another trip up the Appalachian for spring with the Big South Fork National River and Recreation Area as the primary place we would like to explore.
Last July we did our first Appalachian Mountain trip. We had several things we wanted to focus on, the GSMNP, the Blue Ridge Parkway, and the Skyline Drive / Shenandoah National Park while spending as much time as possible on the Appalachian Trail (AT). Our trip was two weeks from home to Dahlonega, GA then a quick stop at the Ocoee Whitewater Center in Tennessee then up to Cherokee and the GSMNP then up the Blue Ridge Parkway and Skyline Drive to Harpers Ferry, WV, to Gettysburg then back down the coast to Yorktown, Cape Hatteras, and then Charleston, SC. We didn't have very much time for trail runs but the only interstate we drove on was from Charleston back home in Jacksonville.
If we were to do this trip again, we would have made only one major change. We would have cut out the coastal return, too many miles with little reward. There is just too much to see on the Parkway and Skyline, we could have returned on the same route and still not have see everything. The traffic, even in mid-July was not a problem with only locals traveling from point A to B on the Parkway being anything close to an issue. We met a number of other Overlanders and lots of great people. As Steve pointed out, there are tons of trails to hike, not only along the Skyline, in the GSMNP and along the Parkway (including the AT).
My recommendation, take your first Appalachian trip up the Parkway and Skyline Drive. This will give you a really good bench mark for what the Appalachians are about.
P.S. Spend a night at the Switzerland Inn in Little Switzerland, NC, your will get some serious brownie points with the wife.