It's hard to give a good general answer, but let's start with an analogy. I've been a faculty member for many years and I have some administrative experience. However, if someone came to me and said "Allen, the Dean is stepping down, and we need you to fill in as Interim Dean of Arts and Humanities," I would feel obliged to say no on the grounds that I understand my limitations and am quite sure that I am not well-qualified. (We'll leave the sorry catalog of my shortcomings to your imagination.) My becoming Interim Dean would be a bad thing for the faculty and students in my College. I would not be able to do the job well (reasons supplied on request!), and so I should refuse to be drafted -- even if Deans were elected by the faculty, and even if there was some reason to think that my colleagues might vote me in.

The generalization is obvious: if someone really thinks s/he is ill-qualified for a certain office, and, let's add, if there are stateable reasons that go beyond possible false modesty, then there's an awfully strong case for saying that the person should decline. Unless the alternatives are even worse, it's hard to see what could justifying saying yes.

Unfortunately, there seem to be people who are not capable of recognizing when they aren't qualified. Some of these people, as it turns out, also have personal qualities that make them attractive to certain parts of the electorate. And so they end up running and sometimes even getting elected.

How culpable are they for not recognizing their own lack of qualifications? That's a tough question, but it seems reasonable to say that the higher the office and the greater the potential responsibility, the greater the obligation to think really hard about one's readiness. Saying "I didn't blink" is almost a sure sign that blinking would have been a good idea.