Need Advice - Depart from Milan or Venice airport?

For sure venice is. Much more interesting city than milan to me. If u have the time, venice for sure.
It can be pricey in and around venice. There are also buses from venice train station to airport andnext town over mestre.

Thank you but we won't have time to visit. Just looking for suggestions as to which is easier to depart from.

Am leaning toward MXP.

Have you checked flights out of Florence? In 2011 I was able to catch a flight out of Florence to Amsterdam to Seattle, all on one ticket through Delta. This year though we caught a Transavia flight out of Pisa to Amsterdam, stayed overnight, then caught the Delta flight to Seattle.

Most of the time you get better connections back to the states out of Milan because it is a larger airport, although with some research you may also find some good flights out of Florence or Venice. On my last night I always find a hotel close to the airport so that I can take the hotel shuttle to the terminal the next morning. Much less stress. In September I'm flying solo into Rome and out of Paris for three weeks. The first hotel room I booked was for the last night of my trip at the Hilton Hotel at Charles de Gaulle Airport (CDG) in Paris, which on a free hotel shuttle is five minutes from the international terminal. I had originally planned that same trip to northern Italy in May by flying in and out of Milan before changing it to September. In doing so I found a Hilton property just four miles (10 minutes) from the Malpensa airport and they provide a free shuttle to the terminal. The link for that hotel is http://hiltongardeninn3.hilton.com/en/hotels/italy/hilton-garden-inn-milan-malpensa-MXPSLGI/index.html. There is also a Hilton property in Venice about five miles from the airport but they do NOT offer a free shuttle. Under no circumstances would I want to be driving to a large European airport very early in the morning needing to turn in a rental car, all the while trying to make an international flight. Been there, done that, and almost missed my flight because of traffic, an accident and road construction. No matter what flight you choose, I suggest you stay close to the airport on your last night in Europe. Good luck.

You realize that Venice is the other side of Italy and a long ways to go for just the airport. I don't think Venice has any or may be a couple of direct flights to the US. So you early AM flight is a connecting flight to another airport in Europe - maybe Milan. So for the basic answer to your question, it would be Milan just because it is a far better answer.

Now to answer questions not asked. From Florence I would look at departing from either Florence or Rome. Much easier than the long trek to Venice

having researched a lot of flights for our trip, I found Milan - MXP to be by far the better deal. Especially to JFK

Thank you everyone for your help. Much appreciated!

It's about the same amount of train time from Florence to Milan, Padua or Rome. A 10.45 flight is going to be easier to get to than a 7.45 flight. It's roughly an hour by bus or train from Milan to the airport. You can easily get there by 7.30-8.00 in plenty of time for your flight. To get to Marco Polo at 5.00-5.30 in the morning, you'd have to leave Padua around 3.30 - 4.00, allowing an hour to drive to the airport and a half hour to return the car and get to the terminal.

Have you considered Rome? You might be able to get a later flight, and go from Florence.

Have you checked into flights out of Pisa? Twice I have stayed in Lucca, and flown out of Pisa in the morning.

I would fly out of Florence, likely the same price as flying out of Venice.
Milan MXP may be a bit cheaper than any othe airport in Italy, but once you consider the time wasted and the cost of going to Milan the day before (the train isn't free), the slight more expensive cost of flying out of Florence may be worthwhile.
Florence has more options than Pisa with traditional airlines bound to the U.S. (Pisa is primarily a low cost airline hub).

I used rome2rio.com to find airlines that fly to Honolulu and see what connections are possible. I did a quick check and flying from Florence or Milan means 2 connections, Pisa only 1, but connecting in New York (ugh), Flying out of Venice is also 1 connection but in Toronto (do they still make you collect your luggage there even if you're in-transit?) or Newark (haven't been there).

The price you pay for living in paradise?

I have a friend in Florence who travels to Honolulu every year with his family (his wife is from Honolulu).
His preferred way is to fly from Florence to San Francisco with Lufthansa/United (1 stop in either FRA or MUC). That is also my preferred way to come to SFO (my home airport) from Florence (my native city).
The Lufthansa (or United) flights from Germany get to SFO in the afternoon (or early evening if via MUC). He prefers to break the trip and stays for the night in a hotel near SFO, then the next day he flies to HNL.
You can also fly to SFO from FLR with AirFrance (1 stop at CDG), with KLM (1 stop at AMS), with Swiss (1 stop at ZRH). AirFrance-KLM are Delta partners. Swiss is part of Lufthansa therefore is a United partner.
If you prefer to fly to Hawai'i via LAX, you have the same options above in terms of flights. However from Rome FCO there is also an Alitalia non stop FCO-LAX (in code share with Delta).
Flying via New York or other Eastern US gateway will greatly increase the length of your trip. Don't do it.