My nemeses has been my expression pedal. My midi controller is reading the position of the pedal, and it is turned down to about 20-25%, taking the balls out of every preset. I know to look for it now, but the first several months of Axe III ownership, it got me really flustered. The other was with the Axe II - I'd do some reamping one night, and then the next time I tried to play with my guitar, I'd get no signal. I spent 45 mins during sound check, trying to troubleshoot my midi connection and monitoring midi traffic because I was certain my controller was turning off the volume.....only to realize I still had the input set to USB!!!!
I watched a video by a user, and saw he had input one beginning his signal chain, but also had USB block in parallel, so he could re-amp and not have to change the input digitally, thereby avoiding the scenario I described. Now, I don't have that issue anymore!