When we head down we generally blast out the 500+ miles the first day by taking 84 & 81 to Winchester, VA. If you don't mind the slower pace you can jump on Skyline Drive or 340 is kind of in between the slow and fast roads.
I would pick up The Blue Ridge right at the beginning in Waynesboro and follow it to the end. As mentioned, we camped at Meadows of Dan the second night and then stayed in Waynesville, NC the next night.
The Skyline has a LOT of deer but not so many on the Blue Ridge cuz they allow hunting on the private land that abuts it. Speed limit is 35 I think on the Skyline and 45 on the Blue Ridge. Don't plan on going much faster. Slow down if you see a white vehicle cuz that's what the LEO's use.
2006 Suzuki DL650