Earlier discussions about spending the last night in Milan have led me to make a note that it is better to choose a hotel near Milano Nord Cadorna station rather than Milano Centrale. Trains from Cadorna are about 15 minutes faster than from Centrale, and the neighborhood is reported to be nicer. What time is your flight? There's lots of transportation out to the airport, but if the flight is early, staying at the airport might be more comfortable.
From which direction will you be approaching Milan by car? Malpensa is over 30 miles from the city. I definitely wouldn't want to drive past Milan all the way to Malpensa to drop the car, then make a roundtrip into the city for sightseeing. If approaching from the south, I'd want to drop the car at a convenient Milan location.