I would rent one from off Venice island, but agree with the above that trains are a fab way to get around and they run to time, are very clean, and very easy to use.
Check out www.seat61.com for some fab tips on using trains in Italy.
If you really do want car hire, then check out all the usual suspects - Avis, Hertz, Europcar, Sixt, Expedia. almost 8 years ago
All the car rental operations are off the island, or across the lagoon as locals say. The name of the town closest to Venice is Mestre... It's the industrial and commercial, non-tourist heart of Venice. I'm trying to remember how I got to the car rental place in Mestre a few years back... Vaporetto to the train station then I think it was a bus to Mestre. It can't have been difficult, I don't do "difficult" when I travel. almost 8 years ago