I went down 4 or 5 years ago in mid to late October, if it rains it'll suck obviously. Leaves on the road in corners can be an issue on areas like 28 with heavy canopy and tight corners . With layers I had a great ride, the only downside was the Blue ridge parkway (cold...more layers) and the leaf lookers, slow cars gawking at the scenery.
The area if beautiful in the fall and traffic is way less than in summer obviously, makes for for great days of riding, as long as you bring the proper gear.