Itinerary Suggestions requested - 22 nights in Fall

Reviewing your towns listed, I would suggest adding a smaller town as a 1-night stay. Many options along your route, or you could select something midpoint between Siena and the Amalfi Coast. The small town experience would round out your itinerary.

I agree with Jean that some time in smaller towns would be nice, but I would suggest adding a night in Siena and doing day trips to some Tuscan hill towns. If you rent a car, in a day you could easily visit Montalcino, Pienza, and Montepulciano, as well as several other towns and places of interest nearby. (I especially enjoyed visiting the Abbey of Sant'Antimo and the town of Bagno Vignoni.) And on another day you could visit Monteriggioni, Volterra, and San Gimignano.

If you don't wish to rent a car, you could still see a subset of these places by bus from Siena. But in any case, I think a third night in Siena is better than a fifth night in Venice. That's just my opinion though. There's really no wrong answer. You've got a great itinerary with lots of time in each destination, more than many travelers are able to do.

Enjoy!

It is much easier to get to the Amafi Coast from Florence as compared to Siena--direct train at 8:14 to Salerno arriving at 12:06; ferry from the nearby Piazza Concordia at 1PM:

https://www.travelmar.it/_download/orari-travelmar.pdf

From Siena train time [one change] is 5:48, arrival at 2:06PM and ferry at 3:30. So increased travel time for the one full day in Siena planned. You might instead consider a day trip to Siena from Florence [by bus].

Scrapping Siena, allocating 3 nights for the Tuscan Countryside with a car, the best approach would be a Hertz rental from Florence dropped in Chiusi [Mon-Sat AM]. First train to Naples at 10:54 [change in Rome] and direct at 11:52; driver to the town of your choice.

Also note that Siena is not favorable for day trips. Siena to the AC IMO a one-night stay is not a good idea.

Spend a day (and night) in Padua -- it's a wonderful old city just about 30 minutes from Venice. Great piazzas, great food, the terrifically powerful Scrovegni Chapel and the Basillica Sant'Antoinio. I was there for 5 days last fall, and I wish I could have stayed longer. The old town is right beside the university, which gives it a great energy and atmosphere.

Such great replies. Lane, Kingdom, Jean and Chiara--THANK YOU. Revised:

3 nights - Venice
3 nights - Florence
Bike tour (Florence to Siena; 1 night)
3 nights - Siena
2 nights - Orvieto
5 nights - Amalfi Coast
5 nights - Rome

Renting a car In Siena and then making our way through Tuscany seems ideal considering AC next. Siena to AC was going to be rough (thanks N_Kingdom) and adding some small towns staying is perfect. Couldn't appreciate the direction and help more.

I would cut back Siena to 2 nights, pick up a Hertz rental at the train station, spend 3 nights in the countryside [perhaps Montepulciano]:

https://www.wanderingitaly.com/maps/valdorcia.html

We arrange our cars by calling up the broker Autoeurope [having the use of a toll feee number]; get zero- deductible collision, which covers any damage to the body of the vehicle. Read this about driving in Italy and restrictions involved [ZTLs]; never leave anything of value in a vehicle when parked:

http://driventoit.blogspot.com/

Train Chiusi to Napoli Centrale, quote to be driven to the AC town of your choice:

www.driveamalfi@hotmail.com

Regarding Orvieto, Autoeurope stopped using Hertz because of complaints; however train time from Chiusi is 29 minutes. Tickets from the tabacchi in the station for the buses and funicular. The latter does not go all the way up to town [but to Piazza Cahen]. Here are the buses:

Bus 1: Railway Station to Piazza della Repubblica.
Bus A: Piazza Cahen to Piazza del Duomo.
Bus B: Piazza Cahen to Piazza della Repubblica.

Cortona [Camucia-Cortona station] a nice day trip. Fixed taxi fare from the station up to the Piazza de la Repubblica is €12.