Given you're both experienced travelers, you'll probably be better off if you stay outside of Frankfurt.
Cologne or Mainz are good recommendations. I personally love Cologne and their spa culture. Great museums too.
May also want to check out some of the Frankfurt suburbs.
On my last trip, I ventured out via the S (or RE) to Hanau which is about 25 km east. Charming town. Particularly enjoyed visiting Phillipsruhe Castle and its museum/art collection. Very Baroque-German.