I think the knob on the right is only useful with the profiling software, but I could be wrong.
What I use the knob on the right for is to have different modes for different occasions. I fly pretty much exclusively, so how I've used it is, on mode 1 stage 1 of the trigger is fire MG's, stage 2 is fire all. On mode 2, stage 1 of the trigger is fire cannons, stage 2 is fire all. I use that one pretty much just for the 109K4 to use my taters/guns efficiently. On mode 3, stage 1 of the trigger is fire all. I use it for flying bombers.
As far as the rest of the controls, I have just about everything mapped to the stick I need to fly. In the software you can set it up so a button can initiate a 'shift state', which basically means if I hold it down, it allows me to map a second function to all the other buttons/switches to do something different. So for example, I have trims mapped to the left hat on the stick. If I hold down one of the buttons on the throttle, the directions on that hat become other things I use a lot but don't need to get to that quickly under pressure, like gear, dive flaps, autoclimb, and fuel tank switch.
The profiling software is extremely flexible. I've heard of people that have problems with it crashing, but it's never once skipped a beat with me.