Yes, I use a real cab with cab sims on. I use the AXE for live only, no recording.
However, cab sims on using a real amp and cab may never sound good with untouched factory presets. Of course I never liked many of the factory presets, the way they sounded to the FOH. I always assumed they were designed more for studio, as a lot of them sound great through in ears and studio monitors.
Shortly after getting the AXE, I read from many of the GURUS here, that you can use the presets as guidelines, but it is better to start from scratch. So that's what I did, I experimented and found amp and cab sims that work well together and tweaked from there. I always worked at gig level. Once I got the tone and gain I wanted, whether clean or heavy, I added effects, WAH, etc. I will say I noticed that using cab sims on, with my setup of a Mesa stereo tube power amp and 4 x 12 cab, introduced a lot of bass into the mix. So I used low cut and turned down the bass level to 2 in the amp block. I chose a cab sim that almost matched my real cab and then adjusted it to match closer. I adjusted the low and high cuts in the speaker section of the amp block and in the cab block to match my cabs specs. Boom, there it was. Using the real cab I have, my best eq cut settings were cut the lows at 110hz and the highs at 5 to 7k, depending on clean to distortion. Don't be afraid to experiment. The AXE has many surprises embedded in it's environment, just waiting to be used.