May Honeymoon - 12 days

Firstly, most of us would count your trip as eleven full days and some jetlagged, sleep-deprived hours on May 2. By the time you get off the plane, through the airport and to Varenna, it may well be after 12 PM, and you'll need to get settled in your lodgings if it's not too early to check in. But Varenna should be a great place to deal with jetlag, and I think 3 nights there when it's your first stop sounds good.

Secondly, I understand the desire to pin down accommodations, but to decide on how many days to spend in each place before you know what you want to do in each city is putting the cart before the horse.

I would want more time in Venice than in the Cinque Terre, but your interests may be different from mine.

I suggest skipping CT. The other 3 give you a variety and let you not always be traveling to the next stop.

Varenna gives you fresh water shore side town, CT the salt water experience. There are differences, but given your limited time, going all 4 places looks like one too many to me. If CT is 'must do' then skip Lake Como. Venice can be as busy or laid back as you want to make it.

I don't think a car would benefit you, what with the car-free zones in Florence and the lack of parking in Cinque Terre - traveling by train and on foot would work fine.

Going straight to Varenna from Milan makes a lot of sense. It is a wonderful place to relax and recovers from all the stress, hustle, and bustle of most weddings. It is easy to get to Venice from there by train, and then on to Florence by train. Consider leaving the Cinque Terre for another trip and just doing those three cities. Also consider the possibility of flying back from Florence. My reason for that suggestion is that it always takes longer to go from Point A to Point B than anticipated. It's not just the actual travel time, it's also the time to pack up, check out of the hotel, get to the train station, get to the new hotel, check in, unpack, and etc. You can easily do all of that without a car -- the train service is great. Love long and prosper.

Congratulations!
All places are great, but you might want to pick only 3 instead of 4. It takes a lot of time travelling between cities, checking in and out of hotels, getting to train stations, etc. Could take up a good part of a day.
Definitely no car! These are cities where you either can't drive, or there is no need to drive.

Thank you all for your input! My gut says I’d rather spend more time in Florence / Tuscany, so I might not do Cinque Terre this time. I’ll probably come back for more advice when I have a bit more planned :-) but this gives me a good start!

We took our honeymoon in Italy 24 years ago. We did just Floence and Rome over 10 days. We spent a whole week in Florence. It was that trip that we discovered just how wonderful staying longer in fewer places can be. The problem with shorter stays is not lack of energy, but time lost in transit and checking in. In fairness unless you are big renaissance art fans, a week in Florence is too much.

I'd choose just three cities: Venice, Florence, and Rome. From Venice you can day trip Padua, Bologna, or Verona. From Florence: Siena, Lucca, and Pisa are all easy. You could also take an organized trip to wine tour or San Giminango. Rome is worth a week easy, but you could visit Ostia Antiqua or Orvieto as day trips as well.

Head for Venice on arrival. Stay one night in Milan before returning. Allocating between Venice, Florence, and Rome is a matter of interests.

I would like to point you at the official Italian Railways website: http://www.trenitalia.com/tcom-en
This is the place to go for train times and to buy tickets. Rail Europe is not held in high regard on this site, it has a reputation for only selling a limited range of tickets, not showing the trains it does not sell and having a markup.

There are certain things you need to know. For example you need to know the "real" Italian names for the towns and stations:
Milano Centrale (Milan)
Venezia S. Lucia (Venice)
Firenze S. M. Novella (Florence)
Roma Termini (Rome) etc.
Tickets are a lot cheaper bought in advance, but once you buy you cannot change your mind which train you get.
Do not buy tickets in advance for your day of arrival, you cannot predict when your plane will land or how long immigration will take. Just buy at the station, and swallow the higher pay-on-the-day price.

For lots more info about the trains, see here: https://www.seat61.com/Italy-trains.htm

Finally, enjoy yourselves!