How long are you there for? I've done a two day stint (one night) before - we needed to be elsewhere in Italy and did a detour. I loved it. As we only had two days we only did two 'sights' - I'm not much of an art buff so we didn't get distracted by any of the galleries, but we did go to the Doge's Palace and to St Mark's Basilica. Both highly recommended (and full of tourists). You can prebook the tickets to both, which means less of a queue (the Basilica is free, but I'm almost convinced we booked tickets and then didn't use them anyway as it wasn't
that busy - the queue wasn't round the block).
If you are staying in the city you at least get it a bit quieter once the day-tripping American tourists have left... Also the day-trippers seem to stick to the Grand Canal. If you wander just off of it, they all vanish.
What we did was on arrival find our hotel, which was wonderfully situated, who gave us a map of the city which was an absolute necessity. It was pretty detailed so you could figure out where all the bridges were and which were dead ends!
I loved just wandering around, it was great. We did walk past a 'bring your own bottle' wine shop (i.e. they sold it out of large barrels into your container) which seemed to be dirt cheap, but we never found it again once we'd procured an empty bottle.
The water tasted awful, but it was really hot when we were there, so we bought mineral water in large plastic bottles.
Mr SavageHoutkop has just asked me to point out that you should leave your bike at home...
Oh, and if you're a gadget type, GPS won't help. We found a stranded couple of tourists who were relying on theirs as a map, except it couldn't get a signal as the lanes/canals are narrow and the buildings quite tall...