The newspaper's web site lists some of the best riverside drives in the USA, and on the list is the Ohio River Scenic Byway from Pennsylvania to Illinois, with a particular liking for the Ohio part. I have to agree on this. Route 7 from Gallipolis to Proctorville and Route 52 from Portsmouth to New Richmond are among my favorites. Route 7 from Hannibal to Marietta is pretty good, too. Plus those road segments have access to two ferries, which are always on my to-do list when I'm anywhere near them.
Parts of southern Illinois are nice, too, by the way.
My bucket list includes the Columbia River, particularly along the northern shore. Before I do that one, I'll have to re-read what William Least Heat Moon wrote about it in Blue Highways.