My wife and I have done both routes and yes the 81 route is longer but its also quieter. What I mean by that is you will have fewer problems on the 81 route than on the 95 corridor. Plus you get to see some beautiful country if you don't mind the extra time.
That being said, whenever we have started our drive on 95 at midnight we've had absolutely smooth sailing the whole way. We do make one stop outside Savannah GA and that takes about 12 hours at an easy pace from the Harrisburg PA area. No rush hour traffic issues as you are between major metro areas during the high volume windows. The only other tip I would give you would be to leave on a Friday night after 11 pm and avoid any rush hour at all.
Have a safe trip!