We've done it a few times. The last time we drove to Charlotte and stayed at the Country Inn and Suites in Huntersville. It was nice with lots of restaurants nearby. It's about 1/2 way to WDW. Did the same thing on the way back, I think. On another trip, we left after work, drove to Beckely, WV and stayed at the Microtel and drove to Kingsland, Ga the next night. Got up extra early and drove to WDW the next morning.
It's not a bad drive and fairly easy to do in 2 days. We didn't kill ourselves. the roads are fine and the scenery is pretty in Va and W. Va.