Is it possible to do Cesky Krumlov as a day trip (I know it would be a long day) from Prague? What would you suggest as the way to get there/back?
Yes, you COULD do it in a day, although spending a night there is fun. We did it by car, from Prague. Left Prague at about 9 AM, had lunch in Cesky Krumlov.
It is not a good idea to do Cesky Krumlov as a day trip from Prague. You will spend at least 6-8 hours getting there and back. I would definitely do it as an overnight trip. But if you insist you can go by train with change in Ceske Budejovice or by bus direct. It's just slightly longer by train.