I highly recommend the trip Bob. Approx 650 miles including the Sky Line drive. Top speed 45 MPH when you can. Set aside at least three days for the trip, a cooler full of picnic stuff. There are quant little motels all along the way.
I,ve made the trip end to end 8 times now, twice in my 64 D200 crew cab, once in the 65 Coronet 500 convertible, twice in Jezebelle, (once towing a pop up trailer), once in the Admiral towing Connie and last July in the 05 Ram towing Connie. Never get tired of it.
A good flip route is US 11 which parallels I-81 or rt 15 up through Virgina. Lots of Civil war history up that way.