Frankfurt to Prague---train or bus?

The fastest is as we did it. By train to Nuremberg then by bus (operated by Deutsche Bahn). But that was not at night. Check Deutsche Bahn website for schedule.

I'd fly...

I would too but they asked if train or bus. We did not fly because all flights were canceled because of snow calamite (but trains and buses /at least some/ were still going).

There's no handy overnight train. But if you really wanted to, you could get a night train departing either Frankfurt Airport or Frankfurt Sud station about midnight and then make a 4 a.m. layover at Regensburg.

Train/bus tickets are cheaper to buy in advance through DB, if you're ready to commit to a date and time and not counting on something less certain, like flight arrival.

If you are going to Vienna on this trip, take the night train from Wien Hbf to Prague. It gets in a bit early but Praha hl n is a big station with all the modern amenities. No good night train option to Prague from Germany, much better from Vienna on the EN night train. The EN night train from Berlin Hbf dep 1901 hrs to Wien Hbf stops in Praha hl n, just before midnight, if that works for you.

I'm just throwing out the flying option as many people don't realize how big Europe is and how cheap it can be to fly.

I am confused, however, by the suggestion to take a night train between Vienna and Prague? That is only a 4 hour-ish ride. Why would you torture yourself in that way?

I agree with Emily that taking night train between Vienna an Prague is not wise. Too close.