We live in Frederick. We generally leave about 2:00 in the afternoon to get through the beltway before rush hour, and stop in Florence, SC. Coming home, we try to leave around the same time and just do everything in reverse. Oh, and we always plan for a quick stop at South of the Border for the kids!
We've got four kids, and flying is just way too expensive! Our kids have grown up used to driving everywhere. We have a DVD player in the car, and that worked well when the kids were younger. Now they are older (8, 10, 13, and 16), so they have their own phones/ipads etc., so they each watch/play whatever they'd like. They are excellent travelers!! I also used to give them little goodies (games, snacks, etc.) as we crossed into each state, which helped to pass the time and give them something to look forward to.
Have you considered the Autotrain? We did that for our trip down last year, and LOVED it! We take it one way and drive the other. It's kind of a nice compromise!