Allow me to direct your attention to section 4.21 of the Tips & Tricks Guide, which is entitled "Organize NPCs with Cast List Topics". In addition, section 4.16 on "Topic Organization" goes into detail on why we believe that using groups to contain NPCs is a bad idea. That's what relationships are for.
Is it "wrong" to do things differently? Nope. However, you will likely run into some major difficulties the moment that an important NPC happens to be the head of the Thieves' Guild AND hold an important position within the Evil Cult. Or perhaps a prominent position in the government. Stuff like that NEVER happens in RPGs, right?
The suggestions we've outlined are specifically intended to smoothly handle a very diverse set of situations that come up across the whole spectrum of campaigns. We've thought through a zillion of these situations and worked out ways to model them well using Realm Works. There's a reason behind all the things we've done with the product. And the ultimate goal is to make your life easier. But every game is different and every GM has a different style, so it's entirely up to you whether our suggestions (and the thinking behind them) are actually the best way to handle things for your needs as a GM. That being said, I strongly urge everyone to first read our suggestions and then make an informed choice of how best to proceed for your game.