M50x mids leave a lot to be desired, that kinda just kills the timbre and mids resolution is just something these don't have even with heavy eq. So it wouldn't take much to be a big upgrade from them, I still think they're decent headphones but need to be priced lower than the $150 or whatever they go for In order to be an ok value IMO. I think the usual heavy hitters commonly mentioned are a worthwhile upgrade.
Sony MDR-1520 - way better timbre, fuller mids, much better instrument separation and imaging, stunning resolution(bass and mids). Comfort is about the same and m50x have a bigger soundstage.
Focal Spirit Pro- much better tonal balance, way more detailed, much bigger soundstage and its accompanying benefits, real bass slam, this is probably the best sounding closed headphone I've ever heard but....the fit sucks, tiny cups and clampy, apparent build quality issues, edgy upper mids
Shure 1540- yeah these aren't neutral, not even close. BUT they are probably the best upgrade for someone who likes the M50x sound, the Shures sound too warm and bass happy, transition from bass to mids is murky and the treble can be a little sharp, but they are super comfortable and the pads are awesome and don't suffer fit issues like the Focals. Where these lack the most compared to the Focal and the Sony aside from tonality is bass detail and resolution. also bass is a little loose and not as controlled as you'd expect given the price, m50x is tighter. They are overpriced new but if you can find a deal they are much better than M50x.
NAD HP50- warmer fuller sound, good detail, much bigger soundstage particularly height, very good treble though needs more air, the m50x sounds very thin in comparison, great bass depth with very tight punchy bass. Some lower treble forwardness that doesn't jive with the rest of the smooth response, much higher clamping force, look weird on the head.
Momentum- it kinda just sounds like someone took the M50x and refined it and pushed the mids up lowered the bass and treble slightly, momentum is more neutral , very very good mids, treble is more laid back but still sounds full with better detail retrieval, bass is a little loose but not as much as the shure, it doesn't do much wrong unlike the M50x except for fit which the earcups are small but more comfy than Focal due to less clamp force but still M50x are roomier and Momentums are hard to wear for longer periods.
AKG K550- the much bigger soundstage, much better clarity, and more neutral (if a bit thin) tonality I think makes it a pretty clear upgrade, more details come through with that better clarity and its also more comfortable. Really curious to try the K545 but I'm afraid the soundstage will be worse and that's pretty much the only thing this has going for it, even so the fact that it's priced essentially the same as M50x and can EQ like a champ make it a no brainier IMO.
NVX XPT100- there's a lot of headphones I prefer over the M50x but a lot of that has to do with personal preferences such as the Sony 1R, UE6000, CAL!, Takstar Pro80 but I don't think those are necessarily better than M50x just different. The XPT100 tho since it's also a studio monitor, deliver better bass definition and tonality while also having fuller and more resolving mids, the treble isn't as smooth as M50x but it has a big comfort advantage and timbre is also lots better. Oh and it's exactly half the price.