Virginia is tough. Given the layout of state lines, most of the significant routes in neighboring states or jurisdictions either pass through Virginia (US-50, I-64, I-95, I-81), don't come close enough to be a serious contender (see below about I-40), or just plain don't seem important enough in the big picture (I-83, North Carolina's I-73 and I-74). I-79 might fall into both of the latter categories.
For that reason, I'm inclined to say I-70. It passes within about 13 miles of Virginia (via US-340 and US-15) in the Frederick area—probably a bit less as the crow flies, but I don't have a good way to measure that—and it's the major route west for a lot of traffic because of people's bias against using non-Interstate routes.
I thought about I-40, but I don't think it passes close enough to Virginia to be a serious contender unless maybe you were to argue that it should have been routed northeast from Raleigh to Norfolk instead of southeast to Wilmington. I'd suggest the latter is more in the nature of "Fictional Highways" because for purposes of this thread, I figure we should take the highways as they are instead of saying "what if." That is, it's one thing if a route extension is planned, like the Autoroute 35 example in the original post, but it seems to me that if a totally different highway is planned in the future, that's a different matter that, for purposes of this thread, doesn't seem to justify saying (in this example) "I-40 should have gone there in the first place."