I'll throw out some random route thoughts -- pick and choose.
First, on the general season. Many campgrounds are going to be closed, bathrooms locked, and water turned off. As a practical matter, I'd suggest approaching this as a bed-and-breakfast or motel-to-motel trip. That means that even though it'll be cool, you'll have to carry more water than you will need to next summer, because resupply will be problematic.
The Blue Ridge Parkway may be closed at any time if there's any freezing precipitation. Still, you may catch a warm and clear stretch of weather where it'll be gorgeous.
From Lake James, if you do decide to ride the Parkway, I'd climb up to Little Switzerland. You'll have a long day's ride into Asheville, another good ride over to Balsam Gap (?) on U.S. 19/74, and then a relatively easy day to Cherokee -- you could stretch it down 19 into Bryson City. Robbinsville is a good day's ride, then over Cherohala (if it's open!) to Tellico Plains. It'll be about a week into Nashville from there; you could take the scenic route, or do a few days' ride going south on the Natchez Trace and back.
Roads in the mountains will be narrow, and some will have lots of traffic. Did I mention it could snow? You might not want to be on the roads after it snows. Even though N.C. does a good job of plowing, there'll be a while where the snow melts, covers the road, and re-freezes at night.
Can you ride, or catch a ride, over to Charlotte and take the Southern Crescent train south from there?
