First off, none of y'all are using the word metaplot correctly. Metaplot is the term used to describe a phenomenon in which time moves forward in the published books and stuff happens. This generally involves the use of signature characters. The most common metaplot phenomena I can think of are in WW games in the 90s and L5R.
What y'all are talking about is plotting a campaign. Not the same thing. Only confusion comes from trying to mix the terms together.
Anyway, to attempt to actually answer the question...
I come up with NPCs whose motivations come into conflict with those of the PCs. When I say conflict, I don't mean that they're a head on collision that can only end in death and destruction.
So if one of the PCs is set on using a one-use magical wonder to heal his son, an NPC might want to use it to heal her granddaughter. Neither has it. Neither has anything against the other person. Both would do anything to make sure their loved one gets better.
Now, combine these with Themes and Threats. Your Themes are your moment to moment things that can pop up at any time and are probably easy to change. Your Threat is probably tied to your big bad.
So, you have the NPCs (hopefully interesting and varied ones) that have motivations that conflict with the PCs. This is set in the backdrop of a Theme or two occasionally spitting out problems for everyone. A step behind that, and you've got some lingering evil, waiting to erupt.
In other words, I never create a rigid framework. No rigid framework will survive contact with the players. Instead, it creates a flexible pool of ideas, with moment to moment, story to story, and overarching suggestions for what might happen next.
You could even tie this into the milestone system to help pace yourself. PC-NPC type conflicts occur in a vacuum in an individual session, so they're associated with minor milestones. Then, once a session goes buy, tie in a Theme. Now you have the confusion of dealing with a Theme and one or more NPCs. Once that story resolves, you've reached a significant milestone. Let this happen once, then during the second time it happens, start dropping hints about the Threat, but don't bring it out. During, say, a third story, bring in the Threat instead of a Theme (or in addition to, if you feel like making life complicated). Let that be a good, hard story, and hand out a major milestone.