It can be done. If you think you're going to need or want to stop overnight, I'd pick Alexandria VA, Florence SC, or Savannah GA since they seem to be nicer areas with better hotels. With the exception of taking Amtrak's Auto Train in 2008, we have driven from the Philadelphia, PA area every trip since 2002. My current strategy is to wake up around 6am the day we are leaving, then go back to bed around 4-5pm and sleep until about 11pm. We leave around midnight and drive straight through on I-95. My wife & kids stay awake that day until we leave, then they sleep in the Avalanche and don't wake up until we are in North Carolina where we stop for gas and a Cracker Barrel breakfast around 7am. We then hit the road again, only stopping for one more gas stop and when bathroom breaks are needed. The trip lasts 16 hours, + or - 1/2 hour. By leaving when we do we miss all of the morning traffic in the northern section of I-95 (especially around the Washington DC area), and when we stop for breakfast we avoid a lot of the traffic during the morning rush. I have tried other departure times, routes, and also stopping for sleep along the way, and have found this current strategy to be the best for us. The long drive and hours aren't a problem for me since I work rotating shifts and spend up to 13 hours a day in a vehicle and am used to being awake all night in a car. I only needed a power nap on two trips and my wife drove for a short time (less than 30-45 minutes) so I could rest. I also drove round trip alone once, and that wasn't bad at all. We get to do it again in 2011.