Driving trip to Italy?

From what I read unless we want to spend time exploring the countryside having a car only makes visiting cities like Venice and Rome more difficult.

You're 100% right in what you said above.
No one here recommends having a car in Rome.
In Venice, if you need a car before Venice and after Venice, then you can just park it in a parking structure on the outskirts, no problem, you just don't use the car while you're there.
But Rome is in a different category from Venice, you don't even want to arrive in Rome with a car.

Are you renting a car in Poland? Can you turn it in and then fly to Rome, then take the train while you are in Italy? Would it be easier to fly open jaw/multi-city and leave Italy for the end of your trip?

Warsaw to Rome - 1800km (1100miles) - EACH WAY !!
Fly if you want to get to Italy and limit your driving to something like ...
Warsaw-Dresden-Prague-Brno-Vienna-Budapest-Krakow-Warsaw (2000km TOTAL)

Thank you for your replies! We will be visiting families in Warsaw and they want to come alone with us to Italy. We will use their cars if we do drive. Flying is an alternative for sure, but I might prefer overnight trains to Vienna, then from Vienna to Venice/Rome. Once off the train what is the common ways to get to hotel/attractions? I need to read up more on train travel I suppose.

djp_syd, my originally idea of a driving trip is similar to what you recommended. But hubby wanted to go to Rome so the distance got extended and a car became less attractive.

Once off the train what is the common ways to get to hotel/attractions?

Depends where.

Most places, walk, take a bus, or a tram, or Métro, or Metro, or taxi.

In Venice walk, take a vaporetto, or hire an expensive water taxi.

My husband wants to drive, so we are considering cutting Rome out of our itinerary. Now the question is if we should still go do to Pisa if we don't go to Rome. The revised rough routes can be either:
Warsaw - Prague - Salzburg - Venice - Vienna - Krakow - Warsaw
or
Warsaw - Prague - Salzburg - Venice - Pisa - Vienna - Krakow - Warsaw
My thought is that we should leave Pisa for when we do eventually visit Rome and/or Florence.

Another destination we are debating is Neuschwanstein Castle. It's 2.5 hours from Salzburg and will give us an opportunity to drive through northern Italy. But it definitely makes the travel from Salzburg to Venice longer and addition will mean we have one day less elsewhere.

One thing to mention is that after Vienna our Polish families might leave us to go back to Warsaw directly, so as long as we spend the 10th night in Vienna they'll be fine with the schedule.

376 miles from Vienna to Venice according to "Travelmath." It seems to me that you've got an awful lot of cities planned for a trip that's only 10 days. As much as it pains me to say it, I'd skip Italy this trip and save it for another time, or take one or two of the other cities off the list. You're going to spend your whole vacation in the car looking out of the window!

Additional responses are on the similar thread under General Europe.

If you leave or drop your car in Vienna you could then mix it up by taking trains.
OBB Austrian Rail operates night train Vienna-Venice.
http://www.oebb.at/en/Travelling_abroad/OeBB_overnight_trains/index.jsp
DB German Rail operates night train Venice-Munich.
http://www.citynightline.de/citynightline/view/en/
You could visit Neuschwanstein from Munich, before heading on to Salzburg (and back to Vienna)

Drive Warsaw - Prague - Vienna
Train Vienna-Venice.- Munich - Salzburg - Vienna
Drive Vienna - Krakow - Warsaw

Thank you for all your valuable feedback. Unfortunately due to various factors I can't really change the mode of transportation or the duration of the trip. At the end we had to settle with a lot of driving. We've managed to limit the driving on most days to be 2-3 hours, and hopefully our experience of driving out of Texas (many hours of driving through extremely boring areas) will make these drives less painful.