I love the G System. It is complicated to set up, but there is a lot of great support available for it. In particular there is a white paper written by Laird Williams that gives a step-by-step guide to all things G.
It also has its limitations and quirks, as does most equipment. In particular, the effects are set up in a particular order in the chain and you can only use one of each type at a time. Also, the relay switching has some delay with some amps (solvable with an Amp Gizmo), and for really high gain amps, it can be a little noisy (solvable with a quiet preamp up front like a Sunday Driver or a Spark Boost).
If you are OK with these, it is an amazing pedal. The internal effects are simply the best quality. It is reasonably flexible. In particular, it is one of very few pedals that allows individual On/Off control of effects within a preset without having to switch modes. The only other high-end unit that does this is a GCX/GCP (which is my other pedal system). It controls amp switching and up to 4 effects. (NOTE: The Mesa pedal is only on the board just in case I have a problem on stage. It's not connected. The reverb pedal is for my acoustic guitar only which doesn't run through the GS, the GS reverbs are great.) I have a couple of gain pedals and a couple of mod pedals in the loops. So I don't have to touch ANYTHING but the G System, and it controls everything else in my rig. I've had it for years and tried other stuff along the way (including my monster rack setup) but so far keep going back to the GS.
You will have to have a 100% series effects loop to use it (not just the G, this is true for any digital loop effects unit). You can read about this in the white paper.
http://www.guitaraffair.com/pdfs/g-system-configuration-and-troubleshooting-guide.pdf