The Midland Trail - If you are coming into W. Virginia from Ohio or Kentucky, travel I-64 and stop at Milton. (Exit 28), where you will find the rather handsome Mud River Bridge as well as the Blenko Glass Factory. I normally come into West Virginia from Ohio, since that's where I live, but I like the drive in along the Midland Trail. One reason is because of the Glen Ferris Inn. It's a cool old place with a lot of history, I like the food, and it's a good place to stay as well. May not be snazzy, but it's down home, a cool place, and done well, and it won't break the bank, and you could find worse places to lodge.
You'll find a lot around this area, but mainly you will look for Kanawha Falls (at Glen Ferris) and a few nice little roadside spills as you come into the area. Leaving Glen Ferris, you will come to Cathedral Falls. This is a place not to be missed and one of the main reasons for following this route. It is probably the single most photographed waterfall in the state, and with good reason. You will believe when you see it.
Leaving Cathedral Falls, travel up SR 16 to Beckwith Rd to view Laurel Creek. There are five or six nice falls in this run. A word of warning. You will want to photograph this place and it is well worth spending some time here, but make sure you are safe. This is a very dangerous stretch with winding curves and people don't drive slow. Additionally, getting into the creek offers a few challenges. There are several places to pull off and park, but, you need to just drive the road first to get a feel for what's a safe place to pull off. Drive up to the top (there's a man made dam/spill and an old service station) turn around and come back and do your parking on the westbound side of the road.
Continue on SR 16 east till you hit US 19. You are now in Fayetteville. Choices are numerous at this point. Turning left is probably a good bet. It will take you on across the New River Bridge, where you can visit the Canyon Rim Visitor's Center, walk out on the overlooks and get a few snaps. If you're still feeling it and ready for some more, just drive on down into the gorge and cross at the Fayette Station Bridge and then up the other side where you can partake of Wolf Creek, Marr Branch, and Kaymoor. Be advised, you are now on one way traffic, but this route will bring you back out on US 19 right where you entered from SR16.
I have compiled a google map of all the falls along this route. It also includes Mill Creek up in Ansted, but that probably won't fit into the day, however, it's worth a visit for sure. Here's a link to the map.