Would love thoughts on a second destination

Venice fits the bill too.

Venice.

We also enjoyed Lake Garda as an alternative to Lake Como. The scenic northern part of the lake starts to lean Germanic, which would add some variety to the trip, and you could day trip to the Dolomites. We saw the Ice Man in Bolzano in a very nice museum, which is also a day trip from northern Garda.

Another vote for Venice. With 4-5 days you can use an entire day to visit Murano and Burano. You could even do a day trip to Padua or Verona. Depending on you level of interest, Verona can be done as a partial day trip while going from Venice to Milan / Varenna. Just a thought to keep the traveling time between destinations to a minimum.

Here's something different. Fly into Zurich, Switzerland. Train to Lucerne, stay for 2-3 days, just gorgeous. Train to Chur, begin the scenic Bernina Express train route, through St. Moritz (stay a day or two) and Tirano, Italy. From there an easy train ride to Varenna.

Venice.

Then why don't you try a new lake? Malcesine or Limone sul Garda, or Stresa on Lake Maggiore. The former is not far from Venice and Verona, the latter is close to Milan Malpensa airport.

I'm limiting my suggestions to Italy, since you posted in this forum.

Roberto,
Please don't leave limit to Italy, I am interested in hearing about anywhere in Europe. We are very flexible as far as going from any city to Lake Como.

I suggest Budapest, even though it's outside Italy.

I have been to Europe 12 times. Only on my last trip did I visit Budapest. I wish I had gone there a decade ago. It's a gorgeous city. Something about Budapest struck me as unusual: The city is very cosmopolitan yet the people were friendly. That's rare. Budapest has a relatively relaxed vibe for such a big city. It's packed with great museums and attractions. The food is among the best I've ever had, rivaling in my eyes even Paris.

If you choose Budapest, I also suggest a side trip to Pecs, Hungary, which is about three hours south of Budapest by train. It's one of the best "small towns" in Europe I've ever been to. Here is my post on it: https://community.ricksteves.com/travel-forum/trip-reports/pecs-hungary

Wherever you go, have a great trip. Cheers.

You might consider going into Lake Como prior to going to Varenna. And that basically limits you flying into Milan since Lake Como's less than an hour away.
Milan Malpensa Airport is an airport serviced by a bunch of airlines. And with the advent of budget European airlines, you can get there from so many cities. For example, you fly into one of these great cities serviced by EasyJet prior to going into Milan:
Amsterdam, Athens, Barcelona, Berlin–Schönefeld, Copenhagen, Edinburgh, Kraków, Lamezia Terme, Lanzarote, London–Gatwick, Madrid, Málaga, Manchester, Marrakech, Munich, Paris–Charles de Gaulle, Prague, Rome–Fiumicino.
Many travelers get very comfortable visiting one place or region and go back time and time again when there are so many other great cities they're overlooking. That's where budget airlines can fill in the void--expanding your horizons to new cities and regions.

A few days in and around Wurzburg, Germany might be a nice change of pace. You'd be at the start (or end) of the Romantic Road (Romantische Strasse) and spending four or five days driving from Frankfurt to Munich could be a really fun trip. The Crime and Punishment museum in Rothenburg is fascinating...

Joe,
As much as I loved Varenna, I agree with Roberto's question here:

Then why don't you try a new lake?

My daughter & I just recently traveled to Annecy, France & now it's one of my favorite places in France.

Annecy is a charming town with a beautiful crystal clear lake, surrounded by amazing mountains ;-)

Have you considered visiting the south of France?

You could fly into Marseilles or Nice, explore the south of France, then end your trip in Annecy, & fly home from Geneva.

Enjoy!

Berlin. Or Torino, which would keep you in northeastern Italy.

Copenhagen

My wife absolutely fell in love with Varenna and Lake Como so I'm not going to question that 😊

We loved Belgium: Bruges, Ghent and Antwerp. Wonderful food; great architecture and art museums; fabulous craft beer; nice people. That one was a pleasant surprise as we didn't expect to be as impressed as we ended up being. We'll definitely be back to do some more exploring of smaller towns!

If you want to stick to trains, Venice is the obvious choice, although I like the Switzerland idea too.

If you don't mind a flight, you can go almost anywhere. All of the places you listed and all of the ones mentioned above by others will have their fans, so you'll just have to throw darts to determine if you want Budapest, Berlin, Barcelona, Prague, Madrid, Vienna, etc, etc.

If you need help deciding, look at weather averages. Realize these are just averages, but for instance, Barcelona will still be quite warm in September, while some other places (say, Amsterdam) can start getting cold and/or rainy.

Sometimes videos are helpful in deciding. Rick's are here: https://www.ricksteves.com/watch-read-listen/video/tv-show

I second Copenhagen or Stockholm very different from your other visit. Or Paris. Copenhagen and Paris are my two favorite cities but Italy is my favorite country.

I am hoping you can tell me about your time in Milan. Where you stayed, where you ate, what you did. I am planning to stay in Milan one day next summer before joining the RS 17 tour of Italy. Thanks Heather

Ciao Joe!

I just returned from a lovely trip to Northeastern Italy, and I would highly recommend Venice, especially the islands of Torcello and Burano. (I've heard from locals that Murano is not worth seeing because it is too industrial and not much glass is produced there anymore). If you're interested in seeing another lake, Sirmione on Lake Garda was wonderful!

Buon viaggio!

Heather,

We stayed at the hotel below, it was a great hotel in a perfect location. Walking distance to the duomo and the galleria plus it has a fantastic rooftop bar.

http://www.deicavaliericollection.com/eng/hotel-dei-cavalieri-milano/index.html

Venice would be my choice.