Venice - where to stay if we are driving

There are several good hotels near Mestre station with easy access into Venice by train or bus. I usually go with Best Western.

I can certainly recommend a very nice villa hotel 20 minutes by train from the station at Venezia Santa Lucia, a place that we stayed this year and have stayed at several times. But it is not in Venice and we did not stay off the islands of Venice until our 5th or 6th visit. IMHO, it is most important to experience Venice when the vast majority of day trippers are not there, at dawn and at dusk to experience the magic of this most magical place. The low light on the ancient buildings along the Grand Canal, the fabulous light in Cannaregio, the romance of the squero in Dorsoduro from across the small rio while having a spritz and cicchetti leaning on the wall of the canal or leaning on the bridge...

There is easy parking in Mestre, there is nearly easy parking on Tronchetto, so drop your car at one of those but if this is your first trip to La Serenissima for goodness sake stay in Venice, whichever sestiere.

Don't hoof it with the bags, use the nicely positioned vaporetti. After all, how else will you be able see the buildings along the Grand Canal?

If you are only staying one night, can you pre-pack an overnight bag and just take that?

Hotel Tritone in Mestre, across from the Mestre station. Very modern rooms and American style air conditioning (I.e. cool is really cool). There is a parking structure next to it and, if I remember, hotel guests get a discount. It was not expensive to park there for 24 hours.
http://www.hoteltritonevenice.com

I would park at Tronchetto and spend your one night right in the city, same as if you arrived by train. As suggested above, you can pack a smaller overnight bag, or at least take some things you don't need out of your bigger bag. Anything you plan to leave in the trunk (not valuables) should be packed and covered before you arrive at the parking garage, so you don't fuss with them on location.

I don't remember what it's called, but we parked in the big parking garage just outside the city and took one of the water taxis in. Our hotel was about a 3 minute walk from St. Marks Square. Venice is much more fun early morning and late at night when the cruise ships leave.