Put her on cruise control and go to back for a nap or turkey sandwich :)
I've not driven ours more than a 4 or 5 hours straight but it is no more tiring than driving a car. As already mentioned, the quality of the road has a major effect on the bumping and noise. It might take you a while to locate and quieten all rattles and noises. To me, the biggest issue is when something in cabinets starts making an irritating rattle. Wife will go to back, locate it and quieten it down by rearranging stuff, putting dish towels between dishes/pots/pans, etc.