Sicily, Venice Rome and Siena italy

It would be best to fly into one city and out the other i.e., Venice and Palermo / Catania. If you fly out of Venice, make sure it’s a late morning flight because getting to the airport is expensive if you need to rely on a water taxi to catch an early morning flight.
You can take a train from the Venezia S. Lucia station to the Firenze S. M. Novella station and change trains to get to Siena (4h 15m). From Siena you can take a train back to Firenze S. M. Novella and switch trains to get to the Roma Termini station (3h 45m).
You can then fly or take a direct, overnight train from Roma Termini to the Cantania / Palermo Centrale stations. Catania takes 11h 15m and Rome takes 13h 15m.

What time of year and how long do you have?

Is the cost of getting home critical?

What is 'the whole family'?

Well, Sicily is not a city. It is a whole large region of Italy. And it can be challenging to travel there unless you rent a car—-but cars for 6 are hard to find. Just something to think about.

So how much time do you have, and what time of year are you going? Sicily is very far south and very hot in summer, and Venice is particularly crowded then too. So spring or fall would be best for your trip.

First, thank you for the input. I have to say I was apprehensive about posting thinking it would be an exercise in futility but was happily mistaken. All the suggestions are appreciated and I am following up on each. To answer some of the questions that were posted above:

All total we are 6 people, my husband and I are both 56 (but the most active of the group) we just returned from 2 weeks hiking in Crete. And have tracked Machu Picchu and Nepal. Then we have our children (and one friend) ages 21, 20, 18, and 14.

We don't have to stay in Siena (we were married there and would like to stay close enough to visit), but anywhere in the region would work.

I would like to limit it to 12 days, I feel only 2 full days is needed in Rome and we are planning on Airbnb's since it is easier on the wallet but works better when you stay longer in each (Cleaning fees and charges).

Any suggestions would be helpful. We are looking to July (because of school) but can move to the end of June if that would affect the cost.

In 2019 my wife and I travelled from Sicily north through Italy, visiting several places (including Rome and Siena) over 3 weeks.
Our itinerary might be useful as reference; it is at the trip report posted on the below link in the Rick Steves' Forum.
We ended at Milan, but it could be adapted to end at Venice instead.
https://community.ricksteves.com/travel-forum/trip-reports/italy-2019-sicily-sorrento-amalfi-pompeii-rome-orvieto-tuscany-siena-florence-cinque-terre-milan

Jeff B from Washington, wow that is impressive but makes me realize I am doing too many places within our time frame. I even wanted to visit my cousin in Genoa (he is the DR for Italy's Olympic swim team and himself an Olympian, Lorenzo Marugo) but fear he will have to visit us.

I am thinking now maybe it is better to set up three main locations (Airbnb) and travel by train to and fro. Like maybe on in Sicily, on in Tuscany or Venice and the last or first in Rome. I recall the first time my husband and I went we did the Rome, Florence, Venice trip and went by train to Siena etc.

I personally would fly into Sicily, your farthest location. Spend 4 nights in either Catania (my choice) or Palermo.

Flight from Catania/Palermo to Venice. Look at Volotea air. 1H40-50 respectively. $60-70.
3 nights Venice.

Train Venezia S.Lucia to Siena 4H12m.
3 nites Siena.

Train Siena to Roma Termini 3H31m.
2 nights Rome.

If you could possibly add 2-4 nights, you would have a much more relaxing trip.

If Sicily stays on your itinerary and you want to go anywhere other than Palermo or Catania with your large group, I’d seriously consider hiring a driver with a minivan. You can’t fit your family into one rental vehicle and large cars are very expensive anyway. Driving and parking a large vehicle in Sicily can be a huge headache. Better to leave it to a professional. And it doesn’t have to be expensive — shop around.

I love Sicily; I spent 17-18 days there back in 2015. With all the wonderful places in mainland Italy, I absolutely would not move a family of six to Sicily for just a very few days. The ratio of sightseeing time to travel time would be too low for me.

Ok, so after all these posts it may be too much to visit all these cities. What if I did Sicily and Florence and did a day trip to Venice?

There are direct trains from the Firenze S. M. Novella (Florence) station to the Venezia S. Lucia (Venice) station (2h 15m). A bit long for a day trip but not impossible.
What I would do once I arrived in Venice is turn left when departing the station and follow the people but take your time. Eventually you’ll work your way to San Marco Square and tour St. Mark’s Basilica.
At dusk hop on a vaporetto (water bus) and take it to the train station stop called Ferrovia. This journey from San Marco’s Square along the Grand Canal will take you back in time as you pass the palaces that line the canal. By taking it at dusk you won’t see the decay on the palaces but instead you’ll see the glorious chandeliers that illuminate its spacious foyers; let your mind wander.
From what I can see on the Trenitalia website the last direct train that departs Venice is before 9:30p.