Transport to airport from Venice early departure.

What does the hotel recommend? That generally is my first question. May have to consider a taxi.

Water taxi official site
https://www.motoscafivenezia.com/en/

Here is the time table for line 5, the ACTV bus that goes to the airport. It looks like the first bus in the morning leaves at 4:35 and is at the airport at 4:56. That seems like it cuts it a bit close for a 6 am flight.
https://actv.avmspa.it/sites/default/files/attachments/pdf/UM/U-5.pdf

Go-Opti Shuttle offers services between the Venice Bus Station (next to train station) through the night and early morning. I did a "test booking " for 4 am and it came out at 30 euros for one person. It there are two of you, it might run about 60 euros for that early morning time. It will be quicker and less expensive than a water taxi even so.
https://www.goopti.com/en

The night service is quite reduced, but Vaporettos in Venice run 24/7. Unfortunately they do not go to the Airport. That service is offered by Alilaguna, a separate private company

Since you are staying close to Venice SL station, I'd just check on Google Maps the walking distance from your hotel to the Piazzale Roma parking lot.

If the walk is doable with luggage in tow, I'd simply ask the concierge to book a land cab. 60 € would border with armed robbery, it's a 15 minutes ride that usually costs around 30 per car, not per person.

Let the driver pick the best departure hour to be at the airport in time to take your flight.

There are two different buses to the airport. The ATVO airport bus begins service from Piazzale Roma at 4:20, arriving at Marco Polo Airport 20 minutes later.

https://www.atvo.it/allegati/aeroporti/linea_35_a_new_dal_9.06_al_29.10.20223303.pdf

If using this service you should plan on walking to Piazzale Roma (over the bridge from the train station area) rather than relying on the vaporetto.

We transferred to a hotel next to the airport the evening before departure. Have dinner in Venice, sleep next to airport. Free or inexpensive transport from there. Not stressful.

I disagree, Piazzale Roma is in Venice and it's 20 minutes away from the airport by taxi. Find an hotel facing the Piazzale parking lot where to stay only on your last day, avoid wasting your last night in Venice dining in an hotel close to the airport.

OP: Are you physically able to tote your luggage from your hotel that is "near the Venice train station" to Piazzale Roma? (And, I'm assuming you mean Venice Santa Lucia train station.)

If yes to the above, just walk to Piazzale Roma in the wee hours of the morning and as noted above catch the first ATVO bus at 04:20. I have taken this bus several times for early flights, and it has worked just fine. One note: the bus won't show up until shortly before 04:20, so don't fret that it's not there at 04:15.

If you can't haul your luggage to P, Roma, do as Dario says and transfer the night before to a hotel right next to P. Roma. I would never trade one more night actually being in Venice for some soulless airport hotel, but that's just me.

Not just you. Many of us feel that way. There is a reason the buses start before 5 am—-they are timed to provide service to the early flights . It is a small airport and it all works out.

hey hey suzanne
like christina posts about the private water taxi: motoscafivenezia.com
we have used them 4 times because of early dark thirty departures. we add it into our cost of vacation and happy to be booked to get to airport before flight. it's a given, even though there are other option, you decide what's best, important and not stressing.
it's been my way of getting to airport the times we have been in venice, even from airport to venice.
they get as close to your hotel as possible and i do not have to pull/lug luggage over bridges, uneven cobblestones, getting lost in alleyways
it's your decision. have a happy vacation, you'll love venice
aloha

Thank you all for your excellent replies. I will check them all out. Nice to know there are options

We did the water taxi from our hotel the the airport. More expensive than other options, but very convenient and fun. You get to go fast in the lagoon and the boat pulls up right at the airport.
Our concierge arranged it for us.

Read what Imboden says: https://europeforvisitors.com/venice/articles/early-flights-from-venice-airport.htm