would appreciate advice on my Italy itinerary

I would consider changing the order, because I would just hate sitting around in the airport waiting for the flight to Milan. (At least compare to the high speed train). You could consider heading directly to Cinque Terre, even though that is a bit of time on the train, but the weather often turns there in mid-October, and the earlier you can go, the better. How long depends on if you just want to see it or what. The minimum would be two nights I suppose.
Then you could take the train to Milan, then head back south and rent a car. Map the drives to all of the towns from various places and see what makes you happy--longer day trips, or more than one base for shorter drives.

What time is your planned flight to Milan? My transatlantic flights have rarely been on time

When planning keep in mind that 2 nights somewhere is only 1 full day because the days on either side are filled with packing, checking out, handling bags, travel, checking in, unpacking etc. I would try to only stay somewhere 1 night for travel or logistical reasons because it doesn't even allow you a full day to explore.

You don't mention staying in Milan. Unless you're flying into Rome from inside Europe somewhere - Fly to Rome, fly/train to Milan, and then train to Varenna sounds like way too much to me in terms of jetlag and dealing with logistics on the ground. Only you know your travel style and tolerances but that sounds like a lot to me.

Some Tuscan cities are easy to access via public transport - Pisa, Lucca, Siena, Arezzo, Cortona - but many of the famous ones like Pienza, Montelcino, Volterra and Civita di Bagnoregio are not. It sounds like you need to narrow down which towns and cities you want to visit and figure out when and for how long you want to have a car.
This is a good basic map of the accesible cities: https://www.wanderingitaly.com/maps/images/tuscany-rail-map.png

Hope that helps, have a great trip,
=Tod

Next we would head to Cinque Terre where I assume we would get there via train and stay there one night/two days (is that enough?)

I think you need at least 2 nights, so 1.5 days of sightseeing.

Any way you can change your original incoming flights and fly into Milan and out of Rome? If the airlines cancel/change any part of your flights, maybe call and ask if such a change is possible. Maybe you'll catch someone on a good day.
And- Lake Como is beautiful, I think you'll really enjoy the area.
Safe travels!

Our flights are non-refundable so we are stuck with flying in and out of Rome. We arrive at 7:20 am which is why i was thinking we should go directly to Lake Como (or Cinque Terre if that makes more sense). I can look in to the fast train but i thought it would make more sense to fly since we are already at the airport.

Non refundable does not always mean non changeable.

One night in CT is NOT 2 days, it is just a half day
( 2 nights equals 1.5 days, 3 nights equals 2.5 days, etc)

Exactly how many NIGHTS do you have on the ground in Italy?

So..we arrive at 7:20 am on Oct. 1 and head directly to Lake Como
3 nights in Lake Como (2 full days);
2 nights in Cinque Terre (1 full day and parts of 2 other days)
5 nights in Tuscany (4 full days)
5 nights in Rome (4 full days)

The latest plan sounds very doable. Go for it!

You have given no clues about your interests; but, in general, your last itinerary looks much better than your first. Planning for driving in Tuscany is tricky, since the roads are mostly narrow and winding. It can take an hour to cover 25 miles. Don’t forget to slot in time for a meal.
I can’t resist commenting on some of your specific choices, especially Civita d B. For reasons inexplicable to me, a few years ago, RS started puffing it as one of his favorite hill towns. At the time, I believe it had just 8 permanent residents. There is nothing there. No beautiful church, no points of historical importance, nothing. Imo, a waste of your quite limited time.
Tuscany and Umbria are filled with beautiful, charming, historically important towns. Find out what some of them have to offer and driving times. (Btw, Asissi, for one, is quite a long drive from some of the others.) Then plan out your days.

My thoughts exactly on Civita d Bag
Don’t understand the attraction at all other than the novelty of visiting a dead hill town

Thank you everyone! I've dumped Civita di Bagnoregio from our itinerary based on your comments. Thank you!!!
My husband has put a wrinkle in my plans. He wants to visit the Ferrari museum in Maranello. So...now I have to decide where to fit that in. We had planned to go from Rome to Lake Como to Cinque Terre to Tuscany (Montepulciano) and then back to Rome. I'm looking at our options and would very much appreciate your input. Here are some options I have identified:
1. We arrive into Rome at 7:20 am and try to make it to Maranello for the 1 hr tour and then on to Lake Como (Varenna) as planned.
2. We go from Rome to Varenna for 3 nights; 2 nights in Cinque Terre and then when we leave Cinque Terre we rent a car and drive first to Maranello and then back to Lucca and then to our hotel near Montepulciano. That seems like a lot of back and forth driving.
3. We go from Rome to Varenna for 3 nights; 2 nights in Cinque Terre and then rent a car and drive to Maranello and back to Lucca and spend one night in Lucca and then head to our hotel near Montepulciano for 4 nights (we had planned 5 nights but it might make more sense to spend one night in Lucca and just enjoy Lucca before we head to the rest of Tuscany),
4. Another option would be to go fro Rome to Varenna for 3 nights and then rent a car in Milan and drive to Maranello and then onto Cinque Terra. The problem is we would just need to park the rental car for 2 days in Cinque Terre and then stop in Lucca on our way to our hotel in Montepulciano.
It feels overwhelming now and I'm not sure how to fit Maranello into the plan, but I know my husband would like to go there. I appreciate your input!!!!