First time to Italy—planning on 3 weeks in October

You will save time by flying into Venice and out of Rome. It can be false economy to do a RT because you then have additional train fares between the cities.

I recommend this order of travel:

• arrive Venice, stay 4 nights
• train to Florence, again 3 nights
• train to Lake Como and Varenna would be a lovely choice for 2 or 3 nights
• train to the Cinque Terre village of your choice, 3 nights (too far to go for less than 3, IMO)
• train from La Spezia to Naples via Rome then on to Sorrento for 4 nights. A long travel day but worth it to be able to wrap up in Rome. This should give you enough time for a day trip to Pompeii, one to the Amalfi Coast, and one day to spare for whatever, including the elusive time to relax.
• train back to Rome for final 4 or 5 nights

This is a fast pace. I would not bother with villas where you are self catering and need a car. Hotels will be your best bet, or B & Bs where you can get assistance as needed. Sometimes when you are in a house, Villa, or apartment you spend a lot of time spinning wheels, trying to get oriented, doing shopping, etc., and have no one to turn to for advice.

If you eliminate one place (Cinque Terre, Como, or the AC) you might add those nights to another stop and slow it down a bit. You can always use more time in Rome and Florence.

You will save valuable time by flying into either Milan to begin at Lake Como or into Venice to begin there. Then work your way south, ending in Rome to fly home from there. Purchase a multi-city flight ticket, not two one way tickets.

Hi, Jane, and welcome to the forum!

First things first: WHY did you choose the locations you have? What about them are of interest to you? "Local flavors" are anywhere and anywhere you go in Italy, if you look for them, but what do you intend to do and see in the places listed? That is a big piece of how long you should stay in any one place, and whether you have TIME to do everything on your list.

Also, you say "I want to see...." but you are traveling with 3 other people. What do THEY want to see? What are THEIR interests? Have you ever traveled with the other couple before? Do you know if their travel style and yours are compatible?

This might be our one chance to see it all.

Nope, you won't see it "all" so best to concentrate on a few top-of-list places first. Trying to cram too much into too few days is expecting weather and everything else to go like clockwork, and is a recipe for exhaustion. The more moves you make, the more sightseeing time and $$ you lose to the transfer process. Also, Is there some reason why you don't think there will be a future trip?

Hoping to stay in villas for several nights throughout. the trip.

What is your idea of a "villa"?

I originally thought we should do Rome first, then head to Como and
work our way down.

Hmmm, I would recommend flying into Venice and out of Rome. The Amalfi is your outlier and will involve backtracking any way you shake it unless you fly out of Naples, and even then there's some backtracking involved.

Do you have a guidebook, and do you have some idea of budget for this trip?