My favorite hotel there is the Venetian, which is a good example of extreme architecture. The Grand Canal is on the second floor.
My favorite clubs are the one in the venetian (sorry, can't remember the name); O.P.M. in Caesar's and the Voodoo lounge on top of the Rio. There's also a club on top of Palms, which has a pretty neat glass window in the floor you can jump up and down on thirty stories up.