Any of the lakes can be reached by public transport. Actually there are very few places in Italy without some form of public transportation (train, bus, or boat), maybe just some place in the middle of a forest.
However based on the fact that you are leaving from Milan (I presume from Milan Malpensa), if Lake Como is not feasible, then Lake Maggiore (and nearby Lake Orta) is the obvious choice, because of the proximity to the airport. Any location along the lake would work. A place near Stresa would allow for an easy ferry crossing the the famous islands (Isola Bella and Isola dei Pescatori). Lake Maggiore is served by trains from Milan. Take a look at a map and see where you would like to be, anywhere is beautiful, especially the western shore on the northernmost part. It is important to realize that no matter which lake you choose (Maggiore, Orta, Como, Garda), the night before your flight you need to be at a hotel closer to the airport because flights to North America are in the morning and transportation from those lake locations may not get you to the airport on time. Near Malpensa airport there are many hotels. If you don't like the idea of spending your last night in an airport hotel in the middle of nowhere, the town of Gallarate is really close to MXP and is a nice town to spend your last night, just 10 min from the airport terminals. Gallarate is on the rail line from Milan to Lake Maggiore, half way between the two. There is a shuttle bus that goes back and forth from the Gallarate station to the airport, but a taxi is not expensive.