M50 is bigger. It's a studio monitor, after all. M50 is only a little bit bulkier than M-100 which looks more svelte. That's all the metal compared to M50's mostly plastic. M-100 weighs a bit less.
Comfort for me is a coin flip. M50 fits me better; M-100 has the memory foam XL pads. They're both comfortable enough for long sessions but neither beats my KRK's.
How do they compare sound-wise? Quite similar, actually. Both have prominent bass between 30 Hz and 150 Hz. M-100 has more bass, about +8-9 dB across that range while M50 has about +5 dB. Both have drops at 5.5 kHz: M50 is ~-10 dB and M-100 is ~-18 dB. Now, before you go "what?" that's a good thing, mostly. This is where vocal sibilance resides, and we humans find tones at around 4.5 kHz to be especially tiring. M-100's -18 dB there is good for a fun-sounding, non-fatiguing headphone. Unfortunately, 5 kHz is vocal presence so the deeper valley there is probably why I get that "behind the drum kit" feel. Both then rise up to about +0-1 dB at 10 kHz for some sheen on cymbals and triangles and such, then both roll off towards 20 kHz. M50 rolls off sharply (down 8 dB) below 30 Hz; M-100 rolls off almost flat (down only 3 dB). M50 has a drop to +1 dB at 75 Hz; M-100 does not. M-100 is smoother through the midrange and above 10 kHz. They're both clean headphones, remarkably so for closed-back cans. Props to HeadRoom for their FR graph overlay.
Plain English translation: they both have similar V-shaped sound signatures. M-100 is smoother, cleaner, has a bit more bass, and has better bass extension along with a few quirks that can be equalized around.
So, yeah, what you're getting with M-100 is a better sounding, better looking, better built M50.