I agree with your point about picking a problem you understand but would add that I would pick a problem you are passionate about as well. Because during the tough times the passion is what carries you through. In building an organic startup you should hopefully be attacking a problem that you both understand well and are passionate about.
I was thinking along similar lines. Paul Graham has done a good job of laying out what the major factors are in building a successful startup, but to pinpoint down to one single factor being the MOST important is really just an exercise in understanding your own weaknesses. For some people, picking a problem you understand is the obvious part, but being flexible about their company's focus is not so obvious, so for them, that will be the most important principle. The most important principles for the individual are the ones that they won't accomplish naturally without thinking about it and working at it.
Sticking with my hypothesis and my principle, I would sway passion first, understanding second. You can go about finding a way to improve your understanding. You can't do that with passion.
