Lots of great inputs so far, especially Skyline Drive: The good news is that you can jump on, drive a section, then jump off.
A lot of the route selection will depend on the amount of time you want to take, how many hours a day you want to drive, etc.
Since you'll be near the beach, I'd say inland for a bit.
I don't know PA that well, but once in WV/MD, Berkeley Spring is a good point to get off the interstate roads for a while, headed south to Winchester, which is a quaint town about 8 hours drive south. Not a back place to stop for the night.
If you want to press on, I recommend Stauton, Va. A few nice old hotels in the heart of the old downtown. Nest place with some great, funky places to eat.
The problem is that if you stay on the interstate, Charleston is only about another 8 hours drive...but 81, while not an ugly drive scenery-wise, is a major north/south trucking route and a bit of a mess to drive.
The option are many from Winchester/Stauton. I would head south on 81 to Lexington, Va. Stop in, find the old town down and have lunch. Very cool town. On your way out, drive up the hill through Washington and Lee College and take the loop around the Virginia Military Institute: Both campuses are very pretty. Wave to my son at VMI
From there, take the pass up through Buena Vista to Lynchburg. Lots of fun.
From Lynchburg, you can divert to the Appomattox Battle Field, just a short drive away. Well worth the hour or so. Take 29 south when you are done. Nothing particularly awesome about 29, but it is quick. You could probably make Charlotte.
Quick blast to Charleston the next day.
There are, of course, a million variations. Easy to hop on and off the interstate for side drives.
The one resource I find invaluable when I do side trips in the South is Southern Living:
http://www.southernliving.com/travel
Have a great time!