For MathJobs does it matter what you put down for Primary Interest? Is it better to indicate 3 interests rather than one? Does it affect who looks at my file or affect my chances of acceptance in any way? For example, suppose I'm mainly interested in combinatorics but also am interested in algebraic topology. If I just put down combinatorics as my primary interest and nobody in the department does combinatorics, will that make the file worse than if I had put down 2 interests?
When I, as a faculty member, go to MathJobs to evaluate postdoc applications, the first thing I do is to click a link that sorts the applications by research area. That way, I can efficiently go through the applications in my field without having to scroll through the whole database. As far as I can tell, the sorting is done on the basis of the applicant's primary interest. So the answer to your title is yes, your choice of primary interest definitely matters.