We want to go from Prague to Regensburg Germany and spend the night. Then we want to go from Regensburg to Cesky Krumlov and spend another night. Then we want to go back to Prague. Essentially we will be making a big circle. We've thought about renting a car but it seems like such a hassle picking up the car (and returning it) in Prague. Unfortunately there isn't a bus or train that goes from Regensburg to Cesky Krumlov. Does anyone have any suggestions???
I would use a private transfer for this route as it would save a lot of time over train/bus. It is more expensive but sometimes you can do a scenic stop or two en route and make a sightseeing tour of it. Here's a few private transfers to check, mydaytrip, czshuttle, or euroshuttle.
Actually it is very well possible to do this route by train.
Looking at the train planner of the Deutsche Bahn there is a direct train from Prague to Regensburg, taking a little bit over 4 hours. From Regensburg to Cesky Krumlov is less straightforward, but very well possible with two changes (in Linz and Ceske Budejovice), taking some 5h30.
Agree with above poster, that public transport works well for the beginning and ending legs of your journey. It's just the Regensburg to Cesky Krumlov leg that I think might be worth doing by private transfer since it would be faster and fewer transfers.
It would seem that hiring a car in Prague - given that you're starting in Prague and returning to Prague - is the most sensible option.