I personally haven't stayed in Frankfurt for very long. I'd prefer going to Heidelburg (probably 40 minutes or so with one train change) for 1/2 day or longer.
I'd also agree with staying in Munich. Besides tons of things to see/do in Munich it is a convenient location to take day trips from. You can go to a variety of places to see castles or even take a long day trip to Salzburg (less than 2 hrs with no changes).