Really rough itinerary - looking for what makes sense

What a wonderful opportunity you have! My husband and I travel to Italy every year for 2-3 months, so I understand your desire to see everything. Even though you have almost 2 months to see the country (plus a trip to Slovenia), the time will pass very quickly, and you have set yourself a very full agenda. I am assuming that you are flying into and out of Rome but if you could fly open jaw into Venice and out of Rome you would be able to save a lot of travel time. I can only advise you from my only experience, but I would suggest that you break the trip into weekly increments. Your choices are endless, but this may be one example:
Weeks 1 and 2 - Arrive Venice and establish a base for your stay in the area. From that base visit the northwest, including an overnight trip to Ljubljana. Try to be in Ljubljana on a Friday. They hold a great food market referred to as the Open Kitchen and it is not to be missed. Visit Verona, Lake Guarda, Ravenna, etc.
Week 3 - move to the northwest and visit Cinque Terre and Lake Como - Perhaps use Como as your base.
Week 4 and 5 - Move to Tuscany and see all that it has to offer.
Week 6 - Travel to Puglia and visit region.
Week 7 - Move on to the Sorrento, Amalfi, Naples portion of your trip
Week 8 - Rome and home.
See how quickly that went - and I think I have already gone beyond your time limit. The outlier to me is Puglia. Wonder that it is, you may want to save it for your next trip.

Do yourself a favor and build in some down time; travel can be exhausting.

Have a great time.

• Five nights for Lake Como/Verona/Lake Garda seems rather rushed. How many times do you plan to change hotels during that period? I'd choose one of the lakes plus Verona. That might--or might not--free up one day to be added to a different stop. It would allow you to see a lot more of the sights around the lake you have chosen. Your comments about extra days in Rome indicate an interest in gardens. Lake Como has several villas known for their gardens. I think you'd be glad to have more time to see them at a leisurely pace. Folks say the lake boats are definitely the best way to get around Lake Como, because the roads don't afford good lake views. Boats are rather slow. I think you'll find it far more efficient to allot sufficient time at Lake Como to see gardens there rather than planning a side trip from Rome to Viterbo in order to go to Villa Lante. (I did enjoy the gardens at Villa Lante, and Viterbo is a nice, relatively non-touristy city, but there's the travel time to consider.)

• One day in a city the size of Bologna (which is said to have Europe's largest medieval center) is going to have considerable logistical overhead. How many hours will you really have to see the city? If you are just looking for a stopover, I'd choose a much smaller place that you'd have more time to enjoy due to less complex settling-in. Bologna, to me, makes more sense for a longer stay, with or without side trips to places like Modena and Parma.

• Puglia can be visited via public transportation (I've done it twice), but it's not a very efficient way to see a bunch of small towns/villages. Without a car, I believe you'll regret having only 4 days, one of which is to be spent on a day trip to Matera. Puglia is long and skinny; you may well need more than one base there.

• I wonder whether Matera could be visited a bit more efficiently on your way from Puglia to the Naples area rather than as a day-trip from Puglia. I know public transportation to Matera is rather thin.

• I loved Ljubljana, but I agree that it is not a suitable day trip from Venice. It would be too much travel time, and the city needs more than a few hours. There are lots of great side trips from Venice that would give you a much better balance of sightseeing time to transportation time, if you find you are ready for a change of scenery: Padua (though worth an overnight stay), Vincenza, Bassano del Grappa and Treviso to start.

• Perugia and Spello are a lot closer to Le Marche than to Rome, but I suppose that doesn't matter if you don't have a car. There may well be essentially no bus service between those places and Le Marche.

• I haven't been to Le Marche, but I think of it as more of a place to enjoy the scenic countryside. I'm not sure how well that's going to work without a car. Five days is rather a long time...

I just took a quick look, but you really need to group the car-needed places together and keep the cities at the edges. I'd cut something (a few things, as the pace is pretty quick)
Perhaps Rome-CT-Como/Garda (via Milan)-Venice-pick up car for Dolomites, Tuscany, Marche, Puglia, drop car for Amalfi, etc., finish in Rome.

Thanks for the replies and suggestions. Guess I should have bolded and underlined REALLY ROUGH, lol! I know it’s difficult to provide info with this really rough itinerary. So much going on and places to see, especially if we are not sure we will ever get back to Italy.

Decided to head north first - take a cheap flight from Rome to Milan and train Milan to Como. We will have had 24 hours overnight in Amsterdam on the way (purposefully as we love Amsterdam) and arrive Rome 9:30 am. Still looking at changing our flight so we can fly into Milan or Venice and out of Rome.
Narrowed down to Lake Como and Verona, even though now I’ve discovered more about Lake Maggiore! Perhaps just a day trip for Maggiore (narrow gauge train/ferry combo I’ve read about for a full day - Cannobio, Stresa and Locarno - WORTH IT?), and ferry on Garda would be worth our time??? One or the other??? Neither??? I have read so many posts I’m overwhelmed😆
Revisited Ljubljana and you are right, too much travelling.
Trieste/Piran, Padua and Udine/Cividale del Fruili - making Venice a base for a week.

Renting a car for Emilia-Romagna, Tuscany, Umbria and Marche - 2 OR 3 BASES RECOMMENDED FOR THAT?
Looking at your suggestions and thoughts though, saving the south and south Adriatic for another holiday (and forcing ourselves to revisit Italy) will make sense and free up a lot of time.
I like gardens, but not a priority if they take away from beautiful atmospheric countryside, mountains, sea and lakes.
We love historical centres of cities, towns and villages.
Tend towards just wonderfully stumbling through towns and cities, with a map to locate historically significant sights, beautiful galleries, etc.
Main reason for leaving Rome for the end is the heat and the crowds I’ve read can still be unbearable the beginning of September. I realize it will still be busy, as well as Venice and Florence, but won’t have the heat.
Enough rambling for now - bring it on!

Renting a car for Emilia-Bologna, Tuscany, Umbria and Marche - 2 OR 3
BASES RECOMMENDED FOR THAT?

I don't understand this question--the bases will be determined what you want to see. Just take it a section at a time.

Hi valadelphia. Sorry, kinda vague! Just looking for a base for each region or a central base to explore two regions at a time, like Tuscany and Umbria together? Or do you suggest a base for each region makes more sense - so four bases?

If I were going to rent a car in Tuscany, I would stay at an agriturismo for a week, then drive to Florence, turn in the car, and stay in Florence for a week.

There are certainly some locations that would allow you to "straddle" two regions, but it's kinda like throwing darts at this point. You've got plenty of time to read and choose what you want to see. I think you are getting overwhelmed by trying to plan it all at once. Plan each section, then link them together, adjusting as needed.
If it helps, I enjoyed both the coastal (Senigallia, Fano, Sirolo) and interior parts of Marche (Sassoferrato, Ascoli Piceno) I visited.

Don't think Tuscany will not be hot in early September!