Rhine River

"We would like to travel from city to city via the river..." The Rhine is a long river - only parts of it are interesting enough for cruising, actually, the most interesting being the "Middle Rhine" segment between Bingen (north of Mainz) and Braubach (south of Koblenz.) From south to north, this segment requires just 2.5 hours on a sightseeing boat. HERE is the KD cruise line information. This part of the river is full of castles and interesting villages. Spending 2-3 days in this area is a good idea - there are castles to tour, villages to explore, and wine bottles to open. http://www.welterbe-mittelrheintal.de There are many other interesting cities on or near the Rhine between the Netherlands and Switzerland - Cologne, Mainz, Speyer, Freiburg among them. But you'll want to use trains to reach them. Even in the Middle Rhine Valley, you should think of the boats not as transportation for moving from village to village but as a sightseeing experience for one day. Trains run hourly along the river bank and cover the scenic ride from Boppard to Bingen in about 30 minutes. A southbound cruise boat for this stretch would require 4 hours of your time.

Thank you for your knowledgable info. Sounds like the week long Rhine cruises are not the only option. My husband needs to attend a conference in Cologne after our travels so we will definitely get to see that area. While he is at the conference, would it be hard traveling up to the Netherlands to visit friends? Any Hotels or B &B's you would recommend in the area?

Köln is relatively close to Limburg province (the thin slice of the country wedged between eastern Belgium and Germany) by car, although it takes surprisingly long to reach by train. Where do your friends live? There's a few direct ICE trains between Köln and Amsterdam daily, with intervening stops in Arnhem and Utrecht. Other than that direct line, however, most connections between Köln and the Netherlands involve one or more transfers on slower train lines.

I also think you can do pretty well in 2-3 days along the middle Rhine. You can use a KD line boat for part of the trip and the local trains run hourly until about nine (more on weekends). The boat travels a little faster with the current (toward Koblenz and Koln) and slower upstream (away from Koblenz and Koln). If you have extra time, add a day on the Mosel. Trier is a great town (outstanding Roman ruins) and the area is a little less developed (more scenic) than the Rhine. If you like wine, try the dry white wines from the region (we don't really see them much here in the states). The word for dry is trocken (pronounced troken), you can choose dry, medium (halb trocken), or sweet.

The best source of information on this area is Bavaria Ben: http://www.bensbauernhof.com/ His hotel reviews are especially great. I love visiting Cologne and the Rhine River Valley, up to Bacharach. The castles are beautiful, but see one and you've seen them all.
I'd rather spend part of my 7 days elsewhere, i.e. Amsterdam.