I think the sound quality of the Fuze is better than the Zen. The build of the Fuze is better feeling and the controls feel nicer. I think Fuze is a better fit for ambidextrous use, Zen fits neither hand well IMO. The Zen software added some goofy device permanently to my Windows list, and the Fuze did not need one. The memory card integration of the Fuze is far far better than the unfortunate Zen, and it makes the difference to us. We own 3 Fuze and 1 Zen.
Nobody mentioned the Zen video! Its pixel count makes watching movies distinctly better than Fuze. Apparently nobody uses these for movies because the video rippers we are given are nearly non-functional.