I have both the ATH-M50 and the HD280 Pro and should receive a set of HD 380's in a few days which I will include in this comparison once I have given them some time.
I collect a large range of music, I listen to rock, metal, rap, electronica, ambient, jazz, blues, reggae.........honestly, you name it, within reason, if it is good quality, I will listen to it.
I would also like to add that there are 2 ways I like to appreciate music, 1) To listen to songs that I love and connect with 2) I enjoy analyzing the audio engineering of the tracks and how well they have been recorded, mixed etc. So I have music in my collection that i listen to for reasons 1, 2 or both. Both of these headphones give me enjoyment in both of the ways I listen to music.
Let me start by saying the 280's and M50's are both good headphones but both have their flaws. Here's how I hear them:
HD280 Pro - Owned for 2-3 years
Great clarity in the mids particularly around vocals and snare type sounds, sometimes a little too pronounced. Excellent sub bass, maybe slightly light on the mid bass. There is a good quantity of bass too but not only is there a good quantity of it, it is very detailed, instruments like bass guitard retain their "twang" rather than just sounding boomy (Not a basshead headphone though). They have good instrument separation in the bass to mid range. A little lacking in treble. Small soundstage, very inside your head sounding. A very balanced analytical headphone that will shine with good recordings and show off poor ones. Quite a dry sound. I feel that everything is pretty close to where it should be. I like these. They have changed substantially for the better with time and now have many hours on them, I use these almost every day.
ATH-M50 - Owned for ~6 months
These are almost the opposite set of headphones to the HD280,
Recessed mids makes vocals sound more distant and takes a little more effort to pick out of the mix. I think the recessed mids also remove alot of the strength or impact from the music, eg. Drums have less impact, bass guitars have less twang, distorted/overdriven guitars have less texture. The bass is also the opposite to the 280's, They seem to lack true sub bass in place of slightly exaggerated mid bass, along with less definition. Their bass can sound a bit boomy and flabby at times (I don't feel that I would recommend these to bassheads either, even though they have more bass than the HD280, the quality, lack of sub bass and definition lets them down). This also results in poor instrument separation in the bass to mid range. Where the M50's do well is in the treble range. Nice clear treble with good separation and little harshness. Their soundstage is better too, things sound like they are being projected to you from a bit further away and a little more directional. Nice decay on reverb effects. The M50 probably makes you feel more involved with the music. With such a low impedance they are driven nicely by my iPhone 4s. With such a V shaped response curve they can be quite fatiguing after a while. I am undecided about the ATH-M50, They are by no means a bad heaphone and certainly have their place, they can bring recordings of lesser quality to life, but i do find myself getting bothered by them at times. I definately feel that they are overhyped.
Both are comfortable but to me the HD280 are more comforable. They do grip quite hard, however they make me sweat less than the ATH-M50 and the tight grip means i have to readjust them less than the ATH-M50's while doing things around the house. The 280's being lighter also makes them more comfortable than the M50 but probably impacts on their durability. Both headphones have travelled with me and neither has broken yet. I think the M50 has a better build quality though.
Neither benefit extremely from amplification but both have a small amount of improvement. Amp is not really essential for either of these.
It is hard to recommend one of these over the other because they both have their place for me and because of the amount of different music I listen to. All I can say is that I am not really biased toward either and I hope the comparison I have given can help aid in your decision making process when buying either of these headphones.