What I've found is that there's a lot of work involved in learning how to really benefit from all the possibilities of the AxeFX. Disclaimer: I'm totally not there yet.
Facts I totally agree with:
1) Many variables outside the axefx (technique -> guitar -> rest of setup) mean you're not going to be getting the same input to even have a chance of getting the same output with the same settings
Helpful advice I totally agree with
1) Use a preset as a starting point.
2) You stand a much better chance of this starting point being good if it's a simple preset, as " preset overengineering" will tend to address very specific issues with a particular setup, rather than add general qualities.
I'd add my own at this point:
3) Spend a lot of time just using the inbuilt presets. There's so much in there already, and they're the natural showcase for it's capabilities. Once you're comfortable with those 200 odd presets, you'll have a decent idea of a starting point. Which brings me to...
4) I really wish that there were good guides for how to dial in a tone. Ideally a video, by someone who explains their thought making process well. Maybe they're out there, just not well publicized. I've seen one or two videos where (insert wizard of axe here) just dials things up, says "oh this doesn't sound right, I'll add X here" and bam! fixed! For example, when describing a component to the sound you don't like, raise the eq gain there, make it sound truly terrrible, and that way we all know what part of the tone you don't like. But going back to point three, the reason wizard of axe dials in tones so quickly is that he is very familiar with the unit, and I think presets have helped me a lot to become familiar. Especially when the preset is named after a song that I know.