Most of my campaigns are focused on the interaction of PCs and NPCs, often in the context of a sandbox (but not always). I find organization to be a tricky matter here. The methods I have used in my books have generally been either an NPC chapter in alphabetical order, or, the approach I take in my notebook, which I used for Sons of Lady 87, which is to simply include NPCs where they are most relevant. Another method is to organize by sect, which the Sects of the Martial World books do. There isn't a perfect approach as each has its advantages and disadvantages.
This method, suggested by Asen, is an interesting solution to the problem. I quite like how it groups characters by numbers (something I usually limit to locations rather than characters). This method uses numbers with decimals so you can have a number of related characters in the same number category (simply distinguishing them by .1, .2, .3, etc). So you have a character for 1.1, 1.2, 1.3.
I like this because it accomplishes something I would use character maps to achieve (often times I map out relationships in a diagram, usually among NPCs and among Sects). Another method I used was how we did it in Righteous Blood, Ruthless Blades, where every NPC has a part of their stat block dedicated to relationships.