M80 beats the S500 at soundstaging easily, then the S500 beats the M80 at resolution and transparency a bit, mostly resolution. S500 has a more intimate soundstage while the M80 boasts more depth. The M80 has more and deeper bass and a fuller sound with cleaner and substantially clearer treble. S500 has clearer, better-balanced and more fleshed-out midrange, although note that I speak of the S500 using ATH-SJ5 pads instead of the stock ones. With HD25 leatherette pads, the S500 isolates nearly as much as HD25 and has improved bass over the stock pads and SJ5 pads. The stock pads are less comfortable, and they are somewhat in between the HD25 pads and SJ5 pads in how they change the sound. They also bring out a fatiguing treble peak. I think that the vent holes on the inner side of the SJ5 pads are part of what gives them an advantage in improving the S500's sound. They allow the drivers to control more air between your ears and the baffles, which is something that tends to result in improved midrange, treble, and soundstage not to mention alleviating a closed-in sound to an extent. HD25 pads are more closed in, which helps boost and focus the bass.
Vocals are good on the M80 and a bit better on the S500 since the S500 doesn't have the M80's boosted upper mids, which make M80 sound somewhat nasal by comparison although not to the point that your cerebral DSP wouldn't be able to compensate for it after a few minutes. ;D
I think that they are both relatively suited for a wide variety of genres.
Then the M80 looks awesome while the S500 would make my eyes bleed out of their sockets if I looked at myself in the mirror while using them.