I just took that drive, and have a few suggestions. First, take the scenic route, which means skip Ohio, PA, Maryland etc. and pack in as much Kentucky, West Virginia and Virginia as possible. That means jump on I64 in Louisville or wherever. I have taken the other route with the turnpikes, big cities and construction too many times to count. If you do opt for the Great Lakes route, see my posts on Toledo and Pittsburgh and Mike G's excellent recent log of his family trip to DC. Certainly you have seen this.
As for the Mountain Route, I would suggest Frankfort KY and the surrounding area as a stop for the bourbon distilleries and horse farms. Lovely stuff, though there is no bourbon to be had in the mostly dry distillery counties.
Huntington WV is a nice college town on the western edge of WV. It has a distinct and peculiar hot dog and root beer stand culture (chili and slaw predominate), a rusty but revived downtown and a big university (Marshall). Do eat at Frostop, which is only a few miles off the interstate. This is a classic drive-in with very good root beer and pretty good food. Cool place.
Driving through WV, you will see many highway signs with the typical fast food -- plus the intriguing local chain Tudor's Biscuit World. Trust me when I say get the Mountaineer -- a BIG scratch biscuit with country ham, a fried egg, cheese, and a McDonald's style hashbrown on top. (I see this as deep south meets Western PA/Eastern OH with the spud-on sandwich motif.) It might be worth getting off to look at the New River and/or the Greenbrier if you haven't seen either before. The former is a white water river at the bottom of an impossibly deep ravine and the latter is like an American Windsor Castle.
Charlottesville and Williamsburg are worthy stops with the sort of cutesy college-town food that, IMO, is never as good as people claim. But both hyper-historical and handsome places are well worth stops. Reid's, an old-fashioned local grocery in C'Ville has a large selection of country hams at absurdly low prices. I got one in my gaze right here.
In Norfolk, you must seek out Doumar's, another old drive-in. They claim to have invented the ice cream cone. I said "I thought that happened at the St. Louis World's fair." Well, yeah, but it was Mr. Doumar of Norfolk who introduced it there. The original machine is still in use 100 years later. The food here is very, very good. Pulled pork and house-ground burgers with double cheese are about as good as it gets. Also, the limeade with fresh limes is nearly identical to the Vietnamese drink (that's good). Ironically, the ice cream is not so great.
I intended to do a full-on report with pictures, which I will do at some point. But I wanted you to have my current as-of-last-week info.
Bon voyage.