Where, exactly, are you going in Tucker County?
US 48 is not a bad route. You have about 22 miles or so of two-lane, between I-81 and Wardensville, but it's not a typical mountain road with a lot of switchbacks. The crossing at the state line is fairly gentle. Wardensville is a speed trap, and WV state police are increasingly running radar on the four-lane part of US 48. It's lightly traveled so you will be tempted to drive faster than the 65 mph speed limits. It's true that there aren't a lot of services, but there is a newer Sheetz at Moorefield. There's also a Liberty gas station at Bismarck, at the intersection of WV 42 and WV 93, just off US 48.
If you opt for I-68 and US 220, how do you propose to get to Tucker County? My recommendation would be WV 972 to US 50 to WV 93, then pick up US 48.
I would probably go one way and come back the other, but that's just me.