Early morning flight from Venice - transportation?

We found that same time issue then flying home from Italy so we took a mid day flight to Frankfurt and fly home the next day.

What time is your flight? This will help with the answer. The first bus out of the Piazalle Roma is a 4:40am. This is the ACTV bus (the same people that run the vaporettos). To catch this bus, you will need to catch the "N" vaporetto at 04:00am at the San Stae stop. The regular vaporettos don't begin daily service to get you there for the first bus. The bus will get you to the airport by about 05:10. You can make a 06:30 flight with this schedule. If you have a later flight, you have a bit more breathing room on the bus. The buses from another bus line (ATVO) make their first bus run at 05:00. If you have a flight after 8:00am, you can probably take the No #2 vaporetto to the Piazalle Roma to catch the bus. The other early option, the Alilaguna boat, is really not that early. The Arancio line (Orange) does stop at the San Stae stop but the first boat is at 07:09. That's too late for an early flight. Here's a LINK to the early N vaporetto schedule.

I'm pretty sure that most if not all flights to the US that start out of Venice make you switch planes in another European country. If that's the case with your flight, you only need to arrive at Marco Polo about an hour before your flight, not 2 hours, if that helps.

Yes the flight will go direct to Paris or Amsterdam, so the one hour check in advice is helpful. I didn't realize we would need to ride a bus in addition to the vaporetto. That was the piece confusing me when looking at various time schedules. Another confusing fact is the airport doesn't open until 5 am! It looks like we could book a private taxi that would take us to the airport direct for around 100 Euro. I know the price can be split but we're staying at a VRBO property so don't expect to know anyone else departing for the airport at the same time. Any thoughts on the taxi option?

You've got the taxi option. 100Euros and you'll get a direct ride to the airport and a 5-8 minute walk from the dock to the airport terminal. The taxi will pick you up at any time as close to your hotel as possible. The other option is the vaporetto to the Piazalle Roma which is a vaporetto stop as well as the main bus station for the Venice Islands. The bus opton to the airport will cost about 5Euro for the bus. You still haven't told us your flight time. There could be other options or different departure times from your hotel. There shouldn't be too much confusion about the airport opening at 5:00am. With the first flight out around 6:30am, it's not necessary to open earlier. Same with Florence airport. Same with Pudong in Shanghai, China as we found out. A lot of airports do this.

Most of the affordable options leave Venice around 7 am

A 7am flight is not much better. The No 5 ACTV depatures from the Piazzale Roma are 4:40 and 5:40. The 6:10 departure would be too late. The first two ATVO buses depart at 5:00 and 5:40. The 5:40 departures would be cutting it very close. Hopefully, your flight is no earlier than 7:30 if you want to take the 5:40 departures. Otherwise, I would suggest the 5:00am bus. To catch the 5:00am ATVO bus, I would suggest that you need to catch the 4:21am N (Night) vaporetto at San Stae. You will arrive at the Piazzale Roma at 4:30. The next N vaporetto at San Stae will be 4:40am arriving at the Piazalle Roma at 4:50am. You might be able to make the 5:00am bus but I'd rather take the 4:21 vaporetto and be sure. Early departures out of Marco Polo are quite common. These flights most often go to other larger EU airports to get you on a larger plane home.

We were in a similar situation a few years ago; took a 5:OO a.m. vaporetto and then bus to the airport and made it for a 6:30 flight. Security isn't very busy at that time of the day. I'd check with your hotel; they deal with this sort of thing on a daily basis and can tell you if you can use a vaporetto or if you need a private water taxi. The hotel usually knows how long it takes to get to the airport at any given time of the day. This holds true for hotels in any major city--they usually are dead on in terms of knowing the amount of time needed to get to the airport and which form of transportation is the best.