I have ridden the Southern Appalachian Mountains a number of times and this area has become a choice destination for our vacation. Most importantly you should purchase a map from MadMaps.com of the area I mentioned above. Although not exactly what you had mentioned, I'm giving you an example of my experience.
This map has highlighted routes in different color that describes how long each loop is and what to see along the way. You could combine one or several loops on each day's ride. A must when touring this area.
On my last trip there I rode from NJ down PA and toured WV, eastern KY, eastern TN, northwest NC, northern GA and southwest VA. I rode for 5,000 miles in 2 1/2 weeks. Depending on the weather, some days I rode 300+ miles and on others a bit less. The main reason for my going to this part of the US was to ride those magnificantly, twisty roads.
I never make reservation ahead of time as this is too stressful for me to make those motels on those specific days. I never had a problem finding a room, but I stopped no later than 5 or 5:30 in the late afternoon. I was on the road by 7:00 am and somedays earlier, depending on the excitement level awaiting me on specific roads.
I hope that this will help you and above all enjoy your trip.
Mike