Driving Munich to Prague - any "must see" spots along the journey?

Not small villages, but on that route, if you go northeast from Munich, there are Regensburg on the Danube, and then once into Czech Rep. there is Plzen.
If you go southeast from Munich, there is Passau on the Danube and then Cesky Krumlov, before heading north to Prague.

It depends on what route you take. Going the southerly route by Passau will take you through the Bavarian Forest, which is the third highest mountain range in Germany, after the Alps and Black Forest.

The northerly route goes through the Oberpfaltzerwald, another forested mountain range. Schwandorf has a nice town center.

As Kent suggests - Passau and Cesky Krumlov are the gems not to be missed.

Go to Regensburg. http://www.regensburg.com/ The old town is a UNESCO World Heritage Site. Check out the 500 year-old historical "Wurstkuchl" for a bratwurst semmel (sandwich) with sweet Händlmaier mustard by the old bridge. http://www.wurstkuchl.de/tavern.html Look for the high water marks on the "Wurstkuchl." Get a beer at one of the Kneitinger Gasthaus (local Regensberg Brauerei). I like the one on Arnulfsplatz 3 http://www.knei.de/ This is really local. Lots of small lanes and unique cafes and restaurants to visit. Great churches too. Don't miss the Lieben Frau zur Alten Kapelle: http://www.alte-kapelle.de/htm/altekapelle.html

You could check out Walhalla built by König Ludwig I near Regenburg: http://www.stbar.bayern.de/hochbau/walhalla/

A little out of the way but one of my favorites is a walk along the Danube from Kelheim past the Befeiungshalle on the hill, and then up the hill through what was a Keltisches Oppidum (Roman history here too), back down the hill to get to the small boats that ferry you across the Danube Gorge to the Weltenburg Kloister for beer and lunch (the Kloister brews it's own famous beers). Then take the cruse boat through the gorge on the Danube back to Kelheim. It can be done in a half day. The small boats will be ferrying in warmer months. You can always just take the Danube boat to and from Kelheim to the Kloister. http://www.weltenburger.de
/en/

You could stop in at Landshut: Nice town and castle. Lots of history here, search Napoleon Bonaparte. http://www.landshut.de/

Weiden in der Opberpfalz has a nice marketplatz. Americans are based not too far away in Grafenwoehr training area: http://www.weiden-tourismus.info/

A little bit to the north, but check out the Goldene Street between Nürnberg und Prag. Sorry can't quickly find an English page: http://www.asamnet.de/~patzeltm/goldene_strasse_wb/wb/pages/allgemeines/goldene-strasse.php

A visit in the Bayrishe Wald (Forest) could be fun for sightseeing and hiking. Nationalpark Bayerischer Wald: http://www.nationalpark-bayerischer-wald.de/
Tourist village Bodenmais is popular in the Bayrishe Wald: http://www.bodenmais.de/ Famous area for Glass and Schnapps.

Pilzen is OK, but watch yourself for pick pockets and shady types. You can visit Pilsner Urquell here.

Something unique for US tourists check out the Chodovar Brewery: http://www.chodovar.cz/id101en-hlavni-strana.htm
A little farther north is the bath town of Mariánské Lázně: http://www.marianskelazne.cz/en/ Montgomery had his HQ here after WWII.
Lots of Bath towns in this area of the Czech Republic.

Anyhow there are a lot of things to see in this less traveled area of Germany and the Czech Republic. You will need a toll sticker for the Czech highways

A swing through Passau before turning north could be good too. Passau is impressive.

Hi,

I vote for Regensburg and Kelheim too, see the Befreiungshalle, at least 30 mins hike upwards, on the War of Liberation against Napoleon. Note that the battles and engagements where the Allies lost to les français under Napoleon are omitted from the list. Plzen is also good to see the American Monument dedicated to the liberation of Pilsen by the US in May 1945.

I think you mean Patton at Marienbad in 1945. Montgomery's Tac HQ was in the Lüneburger Heide in May 1945.

If you are just looking for a nice drive along secondary roads through traditional villages and deep forests then I can offer this efficient route that I took several years ago. I did it from Prague to Munich, but I'll reverse it. Head east from Munich to Passau and pick up highway 12. Take hwy 12 north by northeast through the Bayerischer Wald and across the border into the Czech Republic. You are now in the Bohemian Forest. The road becomes hwy 4 in the Czech Republic and it passes through traditional villages and past farms, eventually reaching the small city of Strakonice. There is an old castle there and at the time there was a cafe in the bowels of the castle. From there you continue north northeast on hwy 4, eventually heading right into Prague. Obviously if you want to hit major sites like Cesky Krumlov or Pilsen then you would have to divert from the route.