Last 3-night base - Bamberg or Wurzburg?

Wurzburg. Very easy to go from there to Bamberg, Nurnberg, and Rothenburg via train or auto. Wouldn't classify Wurzburg as a smaller town, but it does have a small town vibe. Plenty of places to have dinner and safely stroll about in the evenings.

I would prefer Würzburg just because of the logistics of getting to FRA in the morning. It looks like there are direct ICEs from Würzburg arriving at the airport at 10:22 and 11:20 (you'll have to take one of those trains from Würzburg anyway, even if you are starting in Bamberg). Those ICEs leave Würzburg at 8:55 and 9:55 respectively. The corresponding connections from Bamberg leave there at 7:41 and 8:41 (a little too early for my tastes) and both have a four minute, cross platform (Gl. 5 to Gl. 4) connection in Würzburg. I think they would hold the ICE at Würzburg for a late regional train from Bamberg, but I'd rather be sure.

In addition to the logistics of the final trip to the airport, Würzburg is a major transportation hub. Bamberg, Nürnberg, and and Rothenburg are directly accessible. Although there are direct regional connections from Bamberg to Nürnberg, Bamberg to Rothenburg would require and extra change in Würzburg.

Würzburg, being larger, would be easier to find accommodations and restaurants.

I would seriously not want to stay somewhere as far from Frankfurt as Bamberg or Wuerzburg on the night before a flight. There's always a faint possibility of major rail disruption.

When we fly out of Frankfurt, we don't even stay in Frankfurt -- we stay at the airport to avoid anxiety about traffic delays. Hilton Garden Inn, just walk across the street to airport check-in.

Thanks all! Very helpful. I'm now leaning toward Wurzburg, as it looks like a more flexible and convenient hub. It's not that I'm sanguine about making it to the airport on the day of the flight; we were in Rome once for an all-day stoppage which was inconvenient, but it was not on our travel day so it worked out OK (though with a lot of extra walking). Funnily, our daughter and her husband were in Germany two years ago and got to the Frankfurt airport at a good time before leaving (after all, they'd arrived there and knew where they were going), only to find out that they'd accidentally booked their return out of the OTHER airport. Chaos ensued, but somehow they just made it there in time. Needless to say, we'll be careful about that mistake! Sometimes it's all too easy to have a plan, but it's the wrong plan:)

only to find out that they'd accidentally booked their return out of the OTHER airport.

What OTHER airport? There is no other airport in or near Frankfurt Int'l airport. I hope they were not mislead into believing that the fraudulently named "Frankfurt Hahn" airport, which is nowhere near Frankfurt, was the airport they wanted.

BTW, in October of last year, we went from Lohr am Main, just west of Würzburg, to FRA to catch our plane home.

The ICE doesn't stop anywhere between Würzburg and Aschaffenburg, so we had to use the RE to Frankfurt Hbf and the S-Bahn from there to the airport. The advantage was that we got off the train at the close-in Regionalbhf, which saved 10 minutes. The 10 minute connection in Frankfurt Hbf went seamlessly and we had no trouble making our flight.

We stayed in Würzburg a night before a flight out of Frankfurt. It did require that we get up very early. There is always a chance for a breakdown in the line or whatever. We thought it was worth the risk to spend an extra night in Würzburg. Würzburg is one of our favorite cities.

You might consider one night in Frankfurt itself or Mainz.

On the 'wrong' airport story, they may have been at Berlin (or Munich?), not Frankfurt. (My mistake, if so. My memory isn't always at the best retention level more than a year later, especially for someone else's story.) I really appreciate all of the advice; it was enough to make a decision for Wurzburg. (Sorry for the lack of umlaut.)