Mosel valley - definitely visit Trier, a beautiful city with substantial Roman bits and pretty much flat (it's right by the Mosel). The museum is good.
Apart from cruising, you can drive along the valley which is quite spectacular, with the vineyards seemingly hanging from cliffs. Koblenz, the city at the junction of the Rhine and the Mosel is very attractive, with a huge fortress on the other bank.
All down the Rhine valley are castles everywhere. It's all wine country so numerous places offer tasting. Mainz has a spectacular cathedral, and across the Rhine is Eltville, a charming Brothers Grimm like town with lots of eating places by the river.
The Weinstrasse through the Pfalz (Grunstadt down to Neustadt - to the west of Mannheim) is very pretty, lots of vineyards and half timbered towns, a good restaurant at the Deidesheimer Hof - access might be a problem.