I just got a MarkV about a week ago.
Just so you know my frame of reference... I've auditioned the QSC K-12 here in my music room and bought the EV- SxA 250 instead, I find the EV to be better, more like a guitar cab and once I had that EV I thought my days of using guitar cabs and power amps were done.
But....
I wanted to try the MarkV because I just had a gut feeling it held most of my favorite sounds so I bought one.
I've been running the AxeFx Ultra into the MarkV in the 4 cable method. I have one preset with no cab or amp blocks, instead it just has tons of effects with the Effects Loop block in the middle. It is excellent as you might imagine since the AxeFx is a world class effects unit even without the amp and cab sims.
I also have set up a lot of my favorite FRFR presets with the amp and cab bypassed with no effects loop in them so without having to change a single cable all I have to do is call up one of those presets and the MarkV preamp section goes silent and the AxeFx preset uses the MarkV as it's power amp and speaker cab. This sounds AMAZING!
On a few I've found the power amp setting (Sag parameter in the amp block) doesn't need to be turned off, the preset sounds great just as it is.
Another really great thing about when you are running the AxeFx preset through the power section of the MarkV is the MarkV has three channels and each of those have there own relationship with the numerous power tubes, depending on how you have the MarkV options selected you might be running through 2 or 4 power tubes, tube rectifier or diode, etc. so when you have the AxeFx running the show you can select channel 1, 2 or 3 on the MarkV and get a slightly different volume level and characteristic to the sound!
I can't imagine using a simple tube power amp and cab for the AxeFx when I can have the MarkV for that role and then also have all the MarkV offers as an amazing and versatile amp in it's own right.
There is only one reason I would consider the QSC K-12 (or, in my case, the EV SxA 250) to be a better choice, that being when I want to have the cab sims from the AxeFx shape the sound I'm after and there have been a few of my FRFR presets that I don't try to adapt to the MarkV because the cab sim was the heart and soul of the presets character and running it through the MarkV's speaker just doesn't represent it well. So far I don't really miss those few presets though, they weren't really anything I used often, they were just there because I could make them not because I really had a use for them.
The MarkV has cut down a lot on my tweaking time and internet tone comparison surfing etc.
I think it is mostly a psychological thing with me, I don't have any doubts that the MarkV sounds like a real amp so I just play the darn thing instead of obsess over every possible tweak and constantly seek out youtube examples of cabinet A or amp B etc. etc.
To give you an overall feel for where the MarkV has put my head regarding gear, I'm seriously considering buying a TC Electronics G system to see if it can replace my AxeFx/MFC-101 in terms of the effects I actually use and just sticking to the MarkV for my amp/cab solution.
I could make enough money off that switch to probably get over halfway to a Suhr Modern which is my latest GAS pain. It will be a very high hurdle for the G system to clear though because the effects and the routing and the control features of the AxeFx are extraordinary. Having the MarkV as my amp for the last week and the AxeFx taking on only the effects role has reminded me of just how brilliant the AxeFx really is. I was so occupied with making sure I was getting a "real tube" sound and busy tweaking every amp block to it's ultimate state that I never really noticed what a great effects unit I had in the AxeFx Ultra! This week it has been put to that task and it has exceeded all expectation!
Anyway, what ever reason a fellow AxeFX user might have for considering the Mesa MarkV I highly recommend it, even if you never plug your AxeFx into it or don't have any desire to replace your AxeFx with it because I think it might just be the only amplifier that can share the top shelf with an AxeFx in someones arsenal of guitar amp sounds. It is a very versatile amp with lots of character. Just as you don't hear all the AxeFx can do for many months of ownership, it is already evident that the MarkV is loaded with many great voices that way as well.
Channel one alone is capable of producing a wide variety of tones that rival +$2000 boutique amps.