You're more of the Venice expert than I am, and I'm a little confused. Maybe you can explain this.

These are the choices for Venice <-> airport travel:
(1) Water taxi. Pros: Direct, private and on your schedule. Cons: Takes you to the water dock at the airport, so you have to schlep across to the terminal. Cost: EUR 100.
(2) Alilaguna. Pros: Direct and a lot cheaper than a water taxi. Cons: Only runs once or twice an hour, goes to the water dock. Cost: EUR 12 per person.
(3a) Vaporetto to Piazzale Roma, then ATVO bus. Pros: Cheap, frequent, goes right into the terminal. Cons: You have to get all the way up the Grand Canal and then change. Cost: EUR 6.50 for the vaporetto, EUR 3 for the bus. Discounts available on the vaporetto.
(3b) Vaporetto to Piazzale Roma, then #5 bus. Identical to 3a except that the bus is 5-10 minutes slower but only EUR 1.10.

From the Grand Canal (particularly north of the Rialto Bridge), I'd generally agree that the vaporetto+bus option is more attractive than the Alilaguna option. But from the Lido, where the boat cuts off the corner by heading directly to Fondamente Nove, then Murano, then the airport, it would seem attractive to me. Maybe I'm missing something.

(In our case, we bought Venice Cards at the airport -- turns out we overpaid for them, but hey, there's always a way to soak the tourists. Given that those gave us free travel on the vaporetti and the #5 bus, that's what we used. But the #5 is criminally undersignposted at the airport, including the fact that the departure board for it didn't work when we were there, whereas it did at the other bus stops.)

Oh, and you're right that the Red Line doesn't start until 8am. But the Blue Line has a pickup at the Lido at 3:56am, getting to the airport at 5. That should be enough for a 6:25 flight, though it certainly doesn't give a lot of breathing room.