Rome, Venice, Florence, or Milan

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while Venice is more romantic and calm

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No, not at all. Your timing will be when there are less people there but Venice can get mobbed with tourists. We booked private tours for the big things to do and then would explore side canals to get away from the crush.

Of all those I enjoyed Vwnice the most.
Rome is pretty awesome as well.
But huge.

Florence. For the love of god not Venice. The biggest tourist trap in the world

It departs from Basel, Switzerland.

Yeah, Milan is more industrial. If I were to go to a city in Piedmonte it would be Alba which is much smaller and smack dad in hte middle of one of the great wine regions of the world.

Or go up to Lake Como.

Honestly, if it's your first time you should probably go to Rome to cover your bases on things like the Colosseum, The Forum, St. Peter's, Trevi Fountain, etc...

If you want to get away from touristy stuff you can wander around Trastevere.

It's a tough call between Rome and Venice. If you want to go go go and see as many sights as possible over 4 days, go to Rome. You can also find chill there by hanging out at the various piazzas. Great day trips include Hadrian's Villa and Pompei/Herculeum, though there is plenty in Rome. If I wanted to wander and immerse myself in a culture, I would spend 4 days in Venice. Spend one afternoon in St. Mark's Square but then explore the side streets and hit up happy hour at the cicchetti bars. Explore the other islands nearby.

Venice

But, don't spend all the time there. Take a day wine/food tour of the region. We've twice had a great time with

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Mario is an Italian sommelier, and his American wife Rachael is a cuisine expert. Tours can be as small as 2. They live in nearby Padua and offer tours there as well.

Venice has been a tourist trap for centuries and does it well. There are many tourist treasures. Take the vaporetti (water buses) out to the barrier island (the lido), Moreno (mostly Venetian glass some Chinese) and Torcello (older than Venice w/ Byzantine church).

Check out the studio of painter Tony Green, Louisiana Italian. He splits his time between Venice and NOLA. LINK

Realize that Venice really does not have any vehicle traffic except for a large transportation/logistics area on the western side. You walk, ride the vaporetti, or get a taxi boat. Walking is not handicap friendly

Get a 1st-class train ticket to Basel.

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It will be late November/Early December.

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If you go to Venice, pack a pair of these plastic pullovers for your shoes. You'd be going during the Acqua Alta, i.e, seasonal floods. My ex and I where there for the worst one on record in 2019. It was a madhouse. Had to trek our of the city with our luggage over our heads.

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It departs from Basel, Switzerland.

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Obviously this is a river cruise?

Are you spending time in Switzerland that's planned outside of these 3-4 days in Italy? I'm just trying to think of what I would plan.

The day of your arrival is a tough day, you'll get in tired and likely just have half a day.

I would probably opt for Rome if you have never been to Rome.

But I would also consider something like:
fly into Venice and 2 nights
1 night Verona
1 Night northern italy
1 night (at least) in Switzerland before the trip.