One highlight is the Middle Rhine valley, a UNESCO World Heritage site. It is a picturesque region, has good wines and is crossed by the famous Rheinsteig hiking trail. You can choose either Koblenz or Mainz/Wiesbaden as a starting point to visit that region. From there you have good train connections. There is one line on the right hand side and one on the left hand side of the Rhine, both being served by hourly or less than hourly tacts. And ferries connect both sides of the Rhine.
If you have enough time, you can conveniently combine the Middle Rhine Valley with a visit to one of these cities. If you are in a hurry have a train ride on the left bank of the Rhine, preferably on a slow train from the Mittelrheinbahn or a semi slow train from the Deutsche Bahn. Koblenz to Mainz takes between 1h00 and 1h30 depending on the type of train.
The Moselle (Mosel) valley is nice too. It is different from the Middle Rhine valley, but has the same assets: picturesque landscapes and towns, good wine, hiking trails. Public transport is convenient too. There is a line running along the Moselle connecting Koblenz to Trier. Buses and ferries fill the gaps. The Moselle valley can be easily be combined with a trip to Luxembourg and Trier. And it is just a stone’s throw from the Hahn airport. Just as for the upper middle Rhine valley, the train ride along the the Moselle is quite pleasant. You can travel on a slow train from the Deutsche Bahn. The whole trip from Koblenz to Trier takes between 1h30 and 2h00, depending on the type of train.
If you choose Luxembourg and Trier, why not add to Metz and Saarbrücken, to make it complete? Public transport between the four cities is straightforward.
If you are prepared to travel two hours by coach, you can also consider a visit to Heidelberg: