Please take a look at my itinerary and let me know what you think. My sister and I will be in Germany Oct7-Oct21 and we plan on renting a car. We are both in our late forties and plan on stopping when we see something that we find interesting.
Day 1 fly into Frankfurt, rent car and drive to Rothenburg, spend the night.
Day two and on, visit Heidlberg, Freiburg, drive through the black forest and along the alpine road stopping in Fussen, Oberammergau, Berchtesgaden, Salzburg, ending and flying out of Munich.
We don't know where we are staying or how long we will spend in each place we just want to enjoy our trip, and not be rushed.
Do you have any recommendations for a Rhine river day cruise? How many days should we plan on spending in Munich? Over night in Salzburg or just a tour? Is there any way to fit in Berlin, we were thinking of dropping off our car in Munich and taking a train, or should we just keep the car? I know it is about a 4 hour drive from Munich, or do we just forget about Berlin?
Thanks for all your help

You would really have to hotfoot it to drive from Munich to Berlin in 4 hours. It's really more like 5-1/2 or 6 hours depending on weather, traffic conditions, your driving style, etc. Also about 6 hours by train.

I'd forget Berlin this trip--it's just too far out of the way. Though you could actually fly there fairly easily.

I agree with Rufus to skip Berlin.

Basically, your itinerary looks OK, although you should list it again later to get advise on the pretty routes you may want to take.

Judging by the way you describe your travel pattern, I would suggest you do not plan to drive more than 400km a day, or about 300km as the crow flies. That gives you an idea how far to space your overnights.

How much time in Munich? That's hard to say. I would stay outside of Munich, perhaps in Prien, and trake day trips by car to Berchtesgaden, Salzburg,etc. On days that doen't have the best weather, I would hop on a train and go to Munich for a day. The train Trip takes less than an hour, and the two of you can travel on one Bayernkarte for about 23Euro, as long as you leave after 9AM in the morning. If you want to, you can repeat this trip a couple of more times. Figuring gas and parking if you were to drive to Munich, the cost of these train trips will probably be a wash. You could also take the train fromPrien to Salzburg, but there are some scenic ways to go by car.

There is a pretty back road from Rothenburg to Heielberg, some of it along the Neckar River along the Burgenstyrasse (castle road)

The scenic part of the Black Forest is from Baden-Baden along the Schwarzwald Hochstrasse (Bundestrasse B-462) to Freudenstadt. Another pretty stretch is from Freiburg - Titisee - Domnaueschingen on the B-31. From there you can head toward Meersburg, Lindau, Fuessen.

To answer your Rhein question: For that, I would take the train from the Frankfurt airport to Koblenz. Backtrack on a boat south as far as Bacharach, and then take the train back to Mainz. Stay there overnight and arrange for your car pickup in Mainz. It will be cheaper than at the Ffm airport.

Thank you both for your suggestions. They were really helpful. We kind of thought that Berlin was too much for this trip, guess we will save it for the next time.

Your plan sounds good and realistic---Germany's Black Forest and Bavaria regions are meant to be explored just as you have outlined. If anything, I would suggest stays in Oberammergau and add Innsbruck to your list. If for any reason, you feel the need to get out of Germany, I would head out to Prague. If that is the case, make sure that you tell the rental car agency upon rental that you may be taking the car into Eastern Europe. Is not a big deal at all, but they make a notation on the rental agreement for border authorities. Have a great time! October must be a lovely time to do this.