I’ve done the full length of the drive many times, but I’ve never had the chance to go from one end to the other in one day (mainly because I’d have no way to get back
). A couple of times I’ve done a 2-day version where I start in the middle at Big Meadows. Go north and back on one day, and then south and back on the next day.
There’s basically three rest/replenishment points (or four if you count Skyland.) Elk Wallow (mp 24), Big Meadows (mp 51), Loft Mountain (mp 78 or so). There’s nothing at the south end of the park at 250 except for a seasonal Kettle Korn concession, so if you need supplies you have to ride down a couple of miles into Waynesboro. There aren’t too many places to refill on water, so be sure you have enough to get you to the next wayside store. You could also ride down into Sperryville or Luray at 221, or Stanardsville at 33, but then you have quite a climb getting back up 
It’s a bit hillier on the north half than on the south half, and has better overlooks as well, but the whole thing is wonderful. Traffic is pretty bad this time of year. This is about the time when I stay out of the park because of the leaf peepers. It should be quite safe, but it’s not as fun with all the RV’s and motorcycles buzzing by.
The road surface is quite good and getting better. They’re in the process of redoing the surface south of Thornton Gap (where 221 crosses). The grade rarely gets about 6-7% although there are some spots where it gets to 8 or 9% for very short sections. Descents are generally safe to take at pretty high speed because there are no tight switchbacks.
I actually drive down that way almost every weekend, so I could help with logistics possibly if you need a ride to one end or the other. Hope you have a chance to do it, because it’s tons of fun!