I echo this. You can rent in Duesseldorf and it will only cost you a little more to drop off in Munich. (Like $30.00 or so) If you try to drop off in Salzburg, it will cost you hundreds more. Germany is pretty friendly with their in-country car policies. It all comes down to what makes sense to you financially.

Neuchwanstein is a really cool experience. The scenery there is absolutely amazing. However, the castle interior is largely unfinished. The tour, to me, is a waste of money because of this. The allure for most is because it’s the “Disney Castle”. However, logistically, it’s a nightmare to get to. It will take you 3 times longer to get there by train/bus than simply driving it. So if you find yourself with a car in Munich, it’s worth the extra effort. Personally, for me, I think the Nuremburg is a better excursion and you can easily do it via train.

While I can’t say that I’ve been to every city in Germany, these are my personal experiences:

Duesseldorf: Cool Aldstadt. Next to the Rhine. Not much in the way of scenery

Hamburg- Not a ton to do unless you want to go to the…ahem…”boys town” district. (Reepburg I think?)

Frankfurt- Financial capital of Germany. Interesting city center. Avoid like the plague if you aren’t easily entertained.

Berlin- My favorite city in Germany, and perhaps Europe. So much history there, albeit the town isn’t that old due to WWII. Very liberal vibe and nice English speaking people everywhere. Great food choices.

Nuremberg- Interesting city and reminds me of Salzburg a bit. Very historical for WWII purposes.

Munich/Salzburg- Exactly what you think it is: Picturesq with great beer. Salzburg is so close that it would be a shame to skip it. Salzburg looks like what most Americans think that European cities look like. Excellent scenery and a very walkable city.

Romantic Road- This is an awesome tour if you are driving. The Mrs. will love it. Very gothic cities along the route and it ends in Fussen. Check it out: http://romanticroad.com/