Pre-merger there were few Marriott options. We stayed at the Courtyard near the airport. Admittedly, the view was terrible, but the price was great. I would consider it if paying cash for a hotel and depending how long you are staying (are you arriving from the US and getting adjusted because of time change?). We got a multi-day transit pass (machine at the airport) which included city buses and boats ("vaporetti"). The city bus stop going into the city was a few feet from the front door (opposite side of the street from the hotel). From the bus terminal (actually more like a large parking lot instead of a building), we had a choice of taking the city boats (Vaporetti), private water taxis, the monorail to the cruise terminal, or walking across a footbridge into this historic part of the city. That multi-day pass was worth every penny. We found ourselves jumping on the Vaporetti boats just to ride. One evening we went on a long loop and basically got a tour of the Venice lights and had the most wonderful summer breeze. Then we would ride the bus back to the Courtyard.
In very simple terms think of Venice in two parts-- a medium sized city and then the historic island you have visions of. Buses are on the mainland and Vaporetti boats at the island.
If you are staying after cruise-- by all means get off the ship (you have to ride a monorail type vehicle) and buy the multi-day transit pass at a booth at the transit terminal. Using a combination of the Vaporetti and city bus to get around is easy... and you could certainly use it to get to the airport on your final day. A water taxi directly to your hotel will be "faster" but will also be expensive. The same would be true getting from your hotel to the airport.
Historic Venice is not easy to get around with a lot of luggage. You would probably have to pay a porter to carry your bags through Historic Venice because of the windy sidewalks, steps and bridges. The Courtyard on the mainland near the airport eliminates a lot of the luggage hassle.
Still, now that Marriott has expanded and there are many more offerings, I understand the allure of staying at an historic, plush Palace in the historic area.