Mosel, Rhine or Neckar Rivers

If you won't have a car, the Mittelrhein and Mosel are better served by rail. The Neckar has commuter rail service, but only on one side of the river. You would have trouble accessing Dilsberg, one of the Neckar's highlights, as well as some of the castles, without a car. Also, I think Bad Wimpfen, another highlight, may be on a different rail line, although I'm not certain.

Sorry, forgot to mention that we will be traveling by train and like staying in Bed and Breakfasts vs hotels. Like I said, my first thought was Cochem or Bacarach.

Research where there will be a strassenweinfest nearby on the Mosel, and get a B&B there to experience this unique Mosel valley tradition. In September there should be several in various villages along the river every weekend. We did this in 2010 and had a ball. Our B&B had bikes for rent and there is a level paved bike path along the river in an old railroad bed. And it was the least expensive lodging of the whole trip. A local distrct rail/bus pass was available, so we could bike to the train station and ride the train to Moselkern and hike up to Burg Eltz. Its a little early now, but I do see a weekend festival listed for Sept 12-14,2014 in Traben-Trarbach. It is at the end of a branch line off of the Mosel valley railroad.
http://www.mosellandtouristik.de/en/veranstaltungen/optionalcontent.aspx?url=http%3a%2f%2fweb.deskline.net%2fmosel%2fen%2fevent_calendar&hdl=Calendar of Moselland Events

The Neckar is a pretty nice place, but the Rhine/Mosel area is superior in most aspects.

It would be hard to avoid festivals in September if you are on the Rhine on any given weekend:
On the 1st weekend in September, Bacharach has a wine fest on Sat 9/6.
2nd weekend: Oberwesel from Fri - Mon w/ fireworks on Sat.
3rd weekend: St. Goar from Fr - Sun w/ fireworks on Sat.
4th weekend: Boppard Fr - Sun w/ fireworks on Sat.

I would secure reservations right away for either River.

Do you really have only 2 nights for the area? You'll likely be a little goofy/tired/jet-lagged on your first day and may or may not be up to seeing much, if anything.

I'd suggest 2 nights in Bacharach or another Rhine town - wherever you can find a place that suits you, but stay on the west bank if possible. Then a 3rd day and night in Cochem. From Cochem you can head off toward Paris fairly easily (about 4 hours by train) and move on from there to wherever you're going in Normandy.

If you want to see Castles, stay in St. Goar - Rheinfels is right there. And making a trip to Marksburg, the only never-destroyed castle open for tours along the Middle Rhine, is easy from St. Goar; cross over on the ferry (runs all day) and take the train to Braubach (about 20 minutes.)
Marksburg Castle

If you want wine, stay at a winery in Cochem - like the Weingut Rademacher which is near both the train station and the old town. Reichsburg Castle is right in town, or take a side trip to Burg Eltz.

Really great information. Thanks so much