We have been a few times, I think it is amazing, no where else like it in the world.
Last time we stayed in an apartment beside the Rialto, went shopping in the market which was very fun. There's a very beautiful department store right by the Rialto steps, the building was once owned by the post office I think. It had a fantastic roof terrace cafe/bar, well worth visiting for the view.
The back streets between the Rialto and ST Marks are fantastic to wander through and get lost in. You will get lost a lot, that's part of the charm of Venice. The streets closer to San Marco have the chicest shops.
The Guggenheim is well worth a visit, you can access the front steps from one of the rooms and sit there, right on the Grand Canal for as long as you like, amazing! There's another beautiful museum nearby, the Ca'Rezzonico I think, really stunning
Beside San Marco you'll find boat trips out to the islands, set aside an afternoon for that, really worth doing that trip.
I haven't been out there for years but I remember really enjoying the Lido, you can get a boat/bus over to the island and walk down to the beach.
I'd get a taxi in from the airport, your first glimpse of the city is breathtaking, it really is a sight to be seen.
Hope you have a wonderful time!