Looking for feedback on our itinerary for a 2nd trip to Italy?

I have been to Venice 8 times in the last 46 years. I love the place, but it gets a little old after a couple of days. There are so much other sights to see in Italy.
Have you considered taking a fast train down to Florence and picking up a Hertz car there? It is about 150 miles, and much of the drive is flat--looks like Arkansas. Hertz' city location is 2 miles by taxi from the Florence train station--on Sansovino. Rentals there are less expensive than their airport location. Hertz can give you directions to the road south without getting close to any ZTLs.
You can be in the Tuscan hillside in less than an hour. The countryside outside of Poggibonsi and San Gimignano have a number of nice agriturismos to stay in while doing day trips to places like Siena, Volterra and Certaldo.
The drive down to Umbria is very easy. We find Orvieto to be a very great place to do day trips out of, with great roads that can get you to Perugia and Assisi. Civics is a other interesting hilltown a short distance south of Orvieto.
The Hertz location is across the Orvieto train station, and it is just a 70 minute ride into Rome Termini. Hertz' Saturday hours are limited and they are closed Sundays.
Have a great time.

Wow, you make a great point. It never occurred to me that it'd be a boring drive till we got to Tuscany. The three days in Venice (I'm not counting the travel day we arrive) include a day spent visiting the tiny local islands. Do you think the islands are worth a day and if so, if we left Saturday, is a single day for Venice enough

My second trip included 4 nights in Sorrento, and I felt it was time very well spent! From Orvieto the train would get you to Naples very quick and cheap, then a quick train ride on the circumvesuviana from there to Pompeii, and points south. Sorrento. Amalfi coast. Capri.

I also did Orvieto and Assisi on that trip, excellent choice. I think Assisi to be the epitome of what I expected Italy to be.

Don’t skimp on Venice unless you must, the islands in the lagoon are indeed worth a visit.

Perhaps Arezzo as a base instead of Cortona, returning the car here, then onwards by train.

Wednesday - Arrive Venice (4)
(Pick up car in Venice or train to Florence for car)
Sunday - By car to San Gimignano (3)
Monday - San Gimignano
Tuesday - Day to Volterra By car
Wednesday - By car to Arezzo (2)
Thursday - Day to Cortona by car
(Return car in Arezzo)
Friday - Train to Perugia (3)
Saturday - Day to Assisi by train for last day of Calendimaggio Festival
Sunday - Perugia
Monday - Train to Orvieto (2)
Wednesday - Train to Rome (2)
Friday - Depart Rome

Let's take a step back - what, specifically, about your earlier trip did you find amazing or exciting? The history (a particular era?), culture, art, food, and/or gorgeous scenery? That should help you craft your current itinerary.

We've made a bunch of trips to Italy (every couple of years, one of my husband or I says to the other, "I need to go back to Italy.") Our most favorite locations, probably, are Venice and Rome. Venice because there's nowhere else like it, and Rome because of all the history, all the different eras, and because there's so much to see there that each trip, we visit some places we've been or seen before, plus some new places. And we love the food in Rome.

Look through a couple of Venice guidebooks, and see if the places that appeal to you would take up 3.5 days. I've got to admit, we've made numerous trips there, and still haven't been to the other islands, only partly because husband doesn't like boats. (Except the watertaxi from the airport to our hotel - one of life's splurges that we've made several times.)

I would probably pick up the rental car upon leaving Venice, unless you decide to spend some time in Florence. It's mostly a matter of personal preference, but if I'm going to end up in a rental car anyway, I would rather just rent it from Venice, be able to throw our bags in the trunk, and not have to think about catching a train for the next several days. And yes, the terrain is not that interesting until close to Florence. I would say that once you're in Tuscany, you can visit Volterra, San Gimignano and Cortona all from the same location. We like staying IN San Gimignano because it's so lovely at night and in the morning, after / before the day-trippers are there. And there are a number of good restaurants and great gelaterie there. And because we like to eat at a variety of restaurants and not have to worry about one person not drinking, for the drive home. Staying in San Gimignano, we can walk to and from dinner.

Venice is well-worth 4 nights and yes, the islands are worth a day trip. Rick Steves outlines a nice self-tour in his Venice guide.

I like David's itinerary except I would stay in Assisi instead of Perugia. Two nights in Roma is hardly enough, but you have been there before so maybe it is. I'd skip Orvieto for a nice 4-night stay in Roma myself.

First, I don't think you are spending too much time in Venice. There's a magic to Venice that you only find if you wander the lesser frequented areas and take time to simply enjoy being in this unique place. Walking tours are great, ride the vaporetto up and down the Grand Canal at least once during the day and once after dark. Also, you'll probably be jetlagged and Venice is the best place to just relax and soak it up while you adjust. If you get really tired of it (inexplicably, there are those that never find La Serenissima's magic) you can always day trip to lovely Verona or nearer Padua.

I haven't been to your Tuscan choices, but I loved Assisi and Orvieto. Enjoy!!!

You are definitely not spending too much time in Venice...I've gone 4 times and still would return for more. There is PLENTY to do and see and, if you get sick of seeing sights, then just wandering around is entertainment enough. Every inch of that city is a work of art and because of this I keep returning. The islands are well-worth a full day. I think the length of time you are spending in Venice is a good introduction to the city. You can decide if you want to return again to see more!
I do like the idea of taking a train down south and then renting a car there...it's so easy to take the train and there truly is nothing to see from the motorway. Once you are in Tuscany though, the drives are beautiful and having a car there is FAR superior to public transport.

Picking up from Laurel above ...
Assisi is indeed probably a better choice than Perugia if accommodation costs are not off the scale during festival time. Perhaps 2 nights only though, with the spare night added to Rome.

Friday - Train to Assisi (2)
Saturday - Last day of Calendimaggio Festival
Sunday - Train to Orvieto (2)
Tuesday - Train to Rome (3)
Friday - Depart Rome