The Blue Ridge Parkway idea sounds great! I-81, although it goes through some beautiful areas, can be somewhat stressful, due to the volume of big rigs traveling at high rates of speed. Obviously the BRP will take longer, but if you can spare the time, I think it would be a much more enjoyable trip for you and your wife.
If you decide to go this route, start at Skyline Drive coming out of Front Royal, VA. If it times out, I can even offer you a place to stay near Frederick, MD, about an hour and a half from Front Royal. PM me if you're interested.