Where to go for 2 days between Rome and Frankfurt?

I’d vote Venice.

Munich? Maybe some of the furious Castles in Germany? What have you seen in Europe?

1 2 days isn't much time given the travel time to Frankfurt, but in the right direction you can get a discount flight out of Rome to Budapest (did that surprise anyone?) for under $100 with luggage non-stop.

2 Then to Frankfurt the only option is Lufthansa for about $125; non-stop.

3 Total flight time 3.5 hours (vs 2 hours direct Rome to Frankfurt) then throw in about 5 more hours of airport time and about $100 for the extra flight.

4 Compare all of that to train time and train cost to someplace else in Italy, then you have to be someplace where there is a direct flight on to Frankfurt.

5 That's just one idea, with discount airlines you have all sorts of options.

You can take a direct overnight train from Rome’s Termini station to Salzburg (10h 45m) and sleep in a sleeper car. Store your bags at the train station and spend the day in Salzburg. That evening, take a direct train from Salzburg to Munich (2h) and sleep there. The next day spend your day in Munich’s old town before taking a direct train to Frankfurt (3h 45m) or Stuttgart (2h 30m).

My first thought was Florence, because it's so close by train from Rome. But I think you would find more, cheaper, flights out of Venice for Frankfurt.

How busy will your work schedule be in Frankfurt? Maybe you'd want to spend that time exploring the city prior to being bogged down with professional commitments.

The overnight train from Rome stops in Florence so you could take a direct train from Roma Termini that morning to Florence SM Novella station and store your bags for the day then catch the overnight train to Salzburg at 22:05.

Just to add …we have been to Frankfurt and nearby areas within 2 hrs by train many times over last several years for work (we actually usually stay in Heidelberg when there ;as its closer to work location), and we have added on to those trips seeing Zurich plus nearby towns, London, Strausbourg, France, and Belgium. ;😊

Also Have to consider easy availability of Sunday late
afternoon/evening flights to Frankfurt or Stuttgart from wherever we
go.

1 That's why I thought of Budapest, because I have taken the 6:35pm to 8:20 pm flight to Frankfurt a number of times; but you will burn about 6 hours from Rome hotel to Budapest hotel.

2 The suggestion isn't so much Budapest as it is think out of the box; because you have to travel to Frankfurt, you aren't constrained to Italy.

3 I am not a big fan of overnight trains but given the time constraint, makes sense this time if you can find one to an interesting place with a connection to Frankfurt; maybe Vienna

I would not take the train between Rome and Frankfurt. U will land up spending most of ur time traveling.

I would vote for Venice and surrounding areas - and then take a flight from there to Frankfurt

We will be staying in Regensburg Germany for six nights in between Rome. We were going to fly in to Frankfurt, but we changed it since we can fly to Munich same price