What types of activities do you and your wife enjoy?
I recently spent a quick weekend in FRA and decided to spend the time in Mainz. (Arrived 9AM, departed 8AM next day). The train ride to Mainz hbf is quick (30 min?) and I spent the day checking out a few of the museums, going through the market, taking a walking tour and then heading out in the Altstadt for the evening. I took the early morning train back to FRA and had no problems at all.