Two-week winter trip to Germany

Marilyn just my opinion, but I would skip Frankfurt, and go from airport rail station directly to one of the towns on the Rhine - St Goar or Rudesheim - or maybe Heidelberg. Then Rothenburg only if you stay overnight. Munich, Nürnberg and Regensburg I think are all great places to visit, but all three are larger cities and the last two are similar enough to me that I would pick one or the other not both. I would consider heading south from Munich to the Alps - maybe Garmisch, or somewhere on the Bodensee, for variety. I'd probably give same advice in any season.

You should use the excellent Deutsche Bahn website to get a sample of fares including the variety of discount cards for each trip segment, then add them up and compare to rail pass cost. I like the flexibility of a pass, but if your schedule is pretty fixed and you buy 90 days out, you can get pretty good discounts online.

Since most of your trip is in Bavaria, you can use the Bayern Ticket for a lot of it. Travel after 9 am on regional trains (and buses and local transit) all day for 27 euro for 2, all day on weekends. They are all relatively short distances from each other so there is no big advantage to using ICE or IC trains. Even Frankfurt airport is only 20 miles from the Bavarian border. You do not even need to prebook or reserve the tickets, you can buy them on the day you decide to travel.
Maybe through a spot in the Bavarian or Austrian Alps (but not necessarily a big name resort) for a few days.

Seems decent to me, but you could easily see Rothenburg (and plenty similar towns that haven't morphed into tourist fun houses) as a daytrip from Nürnberg.

Overall, your idea of staying mostly in cities is a good one. One of the biggest limiting factors for touring Germany in the winter isn't necessarily the temperature (many parts of the country aren't usually as cold as you might think) or snow (except for the Alps and some other higher elevation areas, it only usually accumulates in a thin coat that often quickly melts), but the dampness of the air. Meaning, instead of those beautiful technicolor landscapes you see on postcards or travel videos, everything looks rather dull and gray, with often quite limited visibility. This effect is far less pronounced in urban areas, but it means that scenic train or boat rides or drives are not nearly as impressive as in the summer or early autumn. Also, in many of the more popular tourists destinations, some restaurants may close for the season (particularly on the Rhine).

If you decide to head to the Alps in either Bavaria or Austria, you would probably do better to pick a well established resort, rather than a sleepy little town. More of the hospitality-related businesses are likely to remain open in a ski resort. Visit in the middle of the week, and it probably won't even be that crowded.

This is the first time I have used the Travel Forum and I thank each of you for taking the time to respond. You've given us points/suggestions to ponder as we plan.