My usual route is basically Interstate 81 to Interstate 77. Interstate 81 does somewhat go through the mountains, but the terrain is really more like rolling hills than significant grades. Interstate 77 descending Fancy Gap is a significant grade and can be a little trecherous at times due to foggy conditions. They have variable speed limits for that reason. Taking reasonable care and properly downshifting and such are necessary, but if done it's a perfectly good route and in my opinion much preferable to needlessly going through NYC, Baltimore, Washington DC, etc.