You are extremely wise to consider this situation.
You have two factors over and above a normal city to consider. Firstly, how you get from the airport into Venice, and secondly, once you get into Venice, how you find your hotel. Unlike any ‘normal’ city, where a taxi can just pull up directly outside, many hotels in Venice are not so accessible, even by private water taxi. You do not want to be wandering around Venice late at night with your suitcases looking for your hotel.
Option 1: Stay in the airport area, Mestre, for your first night
Depending on how late your flight is, just stay somewhere local to the airport, get up fresh next morning and head into Venice in the day light.
Option 2: If travelling by water taxi from the airport
Provided your hotel is close by to a canal, the water taxi should be able to drop you close to the entrance to the hotel. Taking a water taxi is an amazing experience as you sweep across the lagoon over to Venice. If you can afford the €130 fare, this is one of my top Venetian experiences. If the hotel is not directly by where the water taxi drops you off, ask him to walk you there, especially, if some navigation is required.
You get a normal taxi or bus from the airport into Piazzale Roma (which is in Venice across the rail and road causeway). So, everything as per a normal airport / city experience here. I suggest finding a hotel that is within walking distance of Piazzale Roma. It would be a brave or ill informed tourist, not familiar with Venice, to find the ticket office for the vaporettos and then find the relevant vaporetto stop, never mind finding the hotel once they get off the vaporetto.
Hotels within walking distance are:
Pick of the bunch is the supremely comfortable Sofitel operated Hotel Papadopoli.
The four star Hotel Santa Chiara is the first hotel you will see as you arrive into Piazzale Roma.
The three star hotel, Hotel Canal is 5 minutes further on.