I align with the cutting mat line at the fold, but I also re-check it at every cut, and I verify my eyeballing the fold lineup against the mat by lining up with my 12" sq ruler shoved against the cutting ruler. When I go to cut I slide it sloooooowwwwwly and gently away from the cutting ruler. I also use a binder clip on the far end of the ruler so it doesn't slip that little 1/8 as you get to the end where you are reaching farther and more likely to go astray with the cut.
If my cut did go astray, I re-line it up, then shave it back into a perfect 90 degrees before the next cut.
Whew.