October Italy

1. Train and bus work very well.
2. If you are departing from Rome the next day, it is very smart to stay in Rome the night before. Naples is way to far from the airport. Too many variables that can go wrong getting to the airport. Just about the same for Ovieto. With a car and dropping at the airport is a little easier but still would not do it. The train are very reliable about 95% of the time but you can have delays. If not missing your plane is critical concern, then stay in Rome the night before.
3. Purchasing in advance ONLY to take advantage of discounts that might be available. The Super Economy and Econ tickets are discount tickets but come with restrictions -- generally no exchange and no refund. So purchase if you are willing to adhere to a fixed schedule. However, Regionale train tickets are NOT discounted, never sell out, and should only be purchased in the station (at a ticket machine or window) prior to travel day of or a day or two before.
   

---- and you have been around this site long enough to know that the above is, pretty much, the standard recommendations for your questions.

We always spend our last night near the departure airport and have spent a night at Rome FCO several times.
Orvieto is on the train line so may work. It is also on the Autostrada, an easy drive to FCO.

Frank, When I look at loco2 for Siena to Assisi, I'm finding long train routes, because they route back to Florence. Loco2 supposedly provides bus information, but I'm still not finding anything less than 4 hours between the two.
Really don't want to stay that last night in Rome, but I'm afraid you are right. Would be nerve wracking. No interest in driving a car to the Rome airport. ;)

I agree with staying overnight near FCO. The distance and time from Naples is too risky. If you have a car, you might want to go from Orvieto. A lot depends on the time your flight departs.

Your itinerary seems to require a lot of travel time as well as checking in and out of hotels. How many nights will you be in Italy? The worst thing you could do is have too many one night stopovers that would not let you enjoy and savor Italy. Also, Orvieto and Naples are in opposite directions from Rome. Choose the one that would interest you most.

EDIT: FlixBus runs a once daily bus from Siena to Assisi. The bus leaves at 8:40 AM and takes about 2 hours. Buy the ticket on their website for cheapest fare.

Going in only one direction over several days makes the most time sense. You don't say where you are flying into, but if it is Rome, hop a train to the north end and work your way back. After the tour head to the south end and work your way back. For us, the last night is always adjacent to the departure airport, unless we have a late afternoon departure and we are on a main train line the night before.

https://www.trenitalia.com/it.html

For the Florence-Siena-Assisi-Rome segment just google Italian Bus Lines in Tuscany and you will find lots of references to various bus options.

For example (but no recommendation) -Globalflixbus - : https://global.flixbus.com/bus-routes/bus-siena-assisi?departureCity=6298&arrivalCity=10367&wt_mc=acq.com.FlixBus.sea-nonbrand.google.5707263681.1743610923_68563032952.ad&wt_cc1=non-branded&wt_cc5=%2Bbus%20%2Bsiena%20%2Bassisi&gclid=EAIaIQobChMI3r7cx7Sb4gIVjoCfCh2YywtgEAAYASAAEgIRv_D_BwE

Purchasing tickets a few days in advance once you are local has always worked well for us (i.e. buy the tickets out on the day you arrive). For the first train trip you can track the costs online from afar and see if costs vary much.

We are flying into Zurich and out of Rome. It's all mapped out well up to Rome with the exception of transportation for Siena and Assisi. With the exception of Varenna to Cinque Terre, these are are short train trips, less than what many will do on a day trip. I have 4 days after the RS Rome tour. We want go to Pompei, but not interested in that area beyond a 1 1/2 days or so.

We will be in Italy for quite a long period of time. We have taken quite a few trips to Europe, just not to Italy. I have become pretty good at trip planning/itinerary creation. I didn't put my days down because I didn't want the thread to get bogged down by small changes back and forth re. number of days. We typically do not day trip. I like to see cities in the evenings, and don't like all the backtracking. We are under 60 and don't mind changing hotels. We can do it efficiently because we pack very light, and actually enjoy being in different places. That said, I typically stay places at least 2 days and usually 3 or more.

We are considering dropping Orvieto and maybe going to Hardrians' villa for an afternoon. We plan to spend more time in Umbria and Tuscany on another trip to Italy.

...... No interest in driving a car to the Rome airport...... Of all the things your have considered, dropping a car at the airport is probably easiest thing to do. Just like any Am airport. Signage is very good and just follow the arrows to the rental agency drop zone. The check in procedure is identical to American procedures. Just walk about hundred yards to the airport. I would encourage that before taking a train from either Ovieto or Florence.

@Frank, I've rearranged things. I really wanted to get to Assisi, but I think if I eliminate rural Tuscany and Umbria, I will have more time on another trip and it should eliminate the need for a car on this trip. For anyone interested, my itinerary is as follows:

Chur (1 night)(strictly to position us for the Bernina Pass train route the next day
Varenna (2 nights)
Cinque Terre (2nights)
Florence(5 nights)(might take day trip to Lucca or allocate time to Orvieto
Rome(tour, 7 nights)
Naples/Pompei (3nights)(might spend time on Amalfi coast or come back earlier to Rome if Hadrian's villa seems interesting and doable)
Rome (1 night, if a hotel is convenient to airport)

....Rome (1 night, if a hotel is convenient to airport)..... There are. Hilton is right at the airport and you can walk to the terminal. It is a tad expensive and dull! If was myself, I would spend the evening in Rome at one of the better restaurants for a final dinner. And catch a cab or shared shuttle to the airport in the morning.

Frank, thanks. I did see a lot of hotels by the airport. Is there any chance that there is a charming neighborhood in Rome with reasonably priced hotels within an easy/quick metro/train ride to the airport? I ended up booking a 10:30am flight out of Rome and I definitely want to stay in Rome the night before.

If staying in Rome the last night strongly suggest you consider booking a driver/car such as Rome Cabs. They will pick you up at your hotel and deposit you at the correct terminal. Unless you stay at a hotel near the rail station, you will need to get to the station, then the train trip and then finding the correct terminal all of which takes time. I only did the train to airport once and it took twice as long as Rome Cabs. Not sure what the cost of Rome Cabs is now, I think about 48€, same as standard taxi.

Staying in Rome proper is risky simply because the traffic is unpredictable. We stay in the Lido di Ostia across from the Port of Rome. We like it because it is authentically Roman and it is 10 minutes on a back road to the airport. The front desk helped us get a taxi. Don't know what your budget is, but we loved this:

The Occidental Aran Blu hotel is located on the seafront and only 10 minutes from Fiumicino airport. It is located in the popular town of Ostia, is a design hotel with modern rooms and panoramic sea views.

I don't think there is anything risky about staying in Rome the last night. The Trastevere neighborhood is nice. The train station will get you to the airport in about 30 mins for about 8 euro. It is regional train and not the Leonard Express. The LE is non-stop from Termini. Personally we always stay in the Termini area but it is more commercial with a lot of activity and nice restaurants. Trastevere has a bit more charm.

I've reserved a hotel a couple blocks from the Termini station for our last night. It looked as though there were some interesting places to eat right at the station. I would be up for any interesting restaurant suggestions in the Trastevere neighborhood to consider.