itinerary

https://community.ricksteves.com/travel-forum/trip-reports/san-diego-to-munich-just-getting-there-part-1

Perhaps my Trip Report will have some helpful info.

I suggest you use this Forum to check out other Trip Reports, and just review the last 12 months of posts here under Germany. There's a wealth of info, and questions answered that you haven't even asked yet.

Have fun planning and safe travels!

Rüdesheim is in the Middle Rhine area. Rothenburg is in Franconia. These are two of my favorite parts of Germany though I would not usually link them together in a single trip as I like to minimize my time lost to travel.

Either of these areas would make a great two weeks - they have for us. Time spent with a good travel guide would help you focus if you are so inclined. I like the Michelin Green Guide best for a couple maps at the beginning to help see the grouping of scenic places. I also like Rick's guide. Used versions or library editions of these guides would work.

Near Rothenburg: Würzburg, Bamberg, Aschaffenburg, Nürnberg and Regensburg have been good for us. They are larger than Rothenburg but you can easily walk across the Altstadt center.

The Rhine and Mosel valleys are filled with small towns.

All these places are easily reached by trains.

If you fly into Frankfurt, Rudesheim is not that far away, and would be a good place to spend a couple of days upon arrival to get over jet lag and acclimate.

When you leave you can head to Aschaffenburg, Würzburg, Rothenburg, and other cities in a "straight line" to eliminate losing time back tracking.

Aschaffenburg and Würzburg are larger than small quaint town, but do have a lot to offer. And as long as they are along the way..... Why Not? Google them and see what you think.

Trains work great on the Rhine and in Franconia. But the location of your base town matters. With a week on the Rhine I would want to visit some Mosel towns as well or possibly Remagen or Linz or Bonn, all north of Koblenz. IME the best central, small-town option for a longer stay like yours is probably BOPPARD (charming, old-world, lots of food/lodging options including riverfront establishments.) Outings by train from here are most convenient.

In Franconia, Rothenburg makes for a weak travel base because of its dingle-weed location at the end of a trunk railway. The rail map below makes R'burg's logistical issues clear and explains why NUREMBERG is a superior travel base town.

https://images.gutefrage.net/media/fragen-antworten/bilder/459443150/0_full.jpg?v=1655930239000

I tend to prefer small, non-touristy towns as travel bases. I've used Neustadt-an-der-Aisch (on the main railway between Würzburg and Nuremberg) on separate occasions for multi-day stays. Convenient, very "local", with easy access to other destinations. Click through photos at the site below to get a feel for this town:

https://www.stadtbild-deutschland.org/forum/index.php?thread/5806-neustadt-an-der-aisch-galerie/&postID=182279#post182279

2 weeks? I'd branch out a little with that much time.

How about Dresden and the Saxon region? Loved that town.

Over south of Prague you've got Cesky Krumlov that's worth seeing.

Salzburg's extemely popular--and drinking beer with The Brothers at Augustiner's beer garden is great.

And the town of Andechs southwest of Munich is another brewery run by The Brothers. It's maybe the best of all the brewery beer gardens.

We're more Bavaria and Tirolean travelers than central Germany.

If you want quaint and charming, check out the Half-timbered route in Germany. There are 100s of towns that fit this description. If you are landing in Frankfurt, then check out Limburg, Marburg, Büdingen, Idstein or Michelstadt. Those are my favorite medieval style towns. Büdingen, especially as it still has its' town walls and towers.
https://www.deutsche-fachwerkstrasse.de/en/Homepage.html

We love small quaint and charming towns, food, beer and wine and
relaxing.

I neglected to mention that the two regions Gary Mc and I have suggested - the Rhine/Mosel and Franconia - are two of Germany's most prominent wine regions.

Rhine: https://www.mittelrhein-wein.com/en/mittelrhein-wein-english/wine-growing-region

Wine venues tend to be located in town like this one in Boppard:
https://www.deutschlandgourmet.info/bilder/gross/5710-Restaurant-Weinhaus-Heilig-Grab-Boppard.jpg

Article on Franconian wine:
https://www.vogue.com/article/franconia-germany-wine-region-travel-guide

You can get beer anywhere, but Franconia is thick with beer lovers and independent breweries; Bamberg and Nuremberg are loaded with nice pubs, many of which serve local Franconian dishes.

Consider taking the Romantic Road from Wurzburg to Fussen/Garmisch.

Rothenburg is on the road as well as many medieval walled towns.

https://www.romanticroadgermany.com
It's not too hard to see the reason for the popularity - despite the modern roots of the idea, the tour combines the historic cities of Würzburg and Augsburg with the three medieval walled towns of Rothenburg ob der Tauber, Dinkelsbühl and Nördlingen, and then finishes off with the tourist highlights of Neuschwanstein Castle and the Alps.

Just back from time spent on the Rhine and Rothenburg, 5-6th time there. Altho I could spend the whole 2 weeks there ( 11 days last trip ), I would add at least 1--2 more places. Limburg ( Lahn) has been mentioned and is a nice place. My favorite other town is Gengenbach. Although I was there just 5 years ago, I was stuck by how beautiful the marktplatz is. It has good train links for parts of the Black Forest and Strasbourg to in France is easily visited.

Instead of overtouristy Rüdesheim I recommend Eltville a few kilometres up the river Rhine. Great wine region.

Bamberg offers a world heritage old town with famous Franconian kitchen. Hotel Brudermühle is my recommendation - very nice owner family.

Knowing that it is way to go but Lübeck would complete the view on the different flavors of Germany. If you want it smaller beautiful Schwerin with Pfaffenteich lake and two huge churches or very Stade close to Bremen are my recommendations.