I'm gonna talk about my own current campaign, as I'm having some trouble with it, and maybe I'll "see" some things...
I started with a generic 3-4 level adventure for beginning characters. It involved a ruins site, an "archaeological dig" that was a cover for wererats seeking a demonic book, and a small town/large village with leadership "issues".
I knew I wanted a dragon to be the ultimate villain/boss fight for the campaign. I play a version of 3.5e called "epic 6th" or E6, so my PCs always stay low-level. A dragon will be a MAJOR challenge to them. I also want this campaign to last six months or a year at most, so I don't need TOO much material.
So I began my campaign design by outlining a new region of my campaign world, establishing a small barony without a baron, a kingdom that has its own leadership issues, and a twist on my campaign world's common religious structure, just for fun. I put the generic adventure in place, and then found out who the characters were going to be. I used on PC as the meat of the party's involvement - she's a knightly type, from the kingdom that once controlled the barony, and she's there to see what would likely happen if the kingdom sent in a new Baron to rule the region. So she has good reason to ask questions and talk to people.
Other PCs are a wizard who wants power, a bard who is constantly having to leave places when he's in trouble, and a cleric who has a fascination for historical scholarship.
I decided that I needed a REALLY good reason for why the two major changes in the status quo both happened at once - the ruins of the evil temple are being explored, and the kingdom is sending in a new baron both within weeks of each other. So, I wrote into the history of the area that there was a large, powerful fey creature that helped, 100 years ago, destroy the evil temple that is now the ruins. It swore an oath to the King that it would guard the temple site for 100 years - which has just ended. So now I have a fey being that has just been released from a powerful oath, and it is HUNGRY. It isn't evil, precisely, but nor does it care about humans/demi-humans. It wants a place of unspoiled nature to dwell in, and sees the barony as just needing a little cleaning out to be perfect.
The dragon - she lives about 100 miles away right now, but she's about to settle down for a few years and lay her clutch. She wants a nice safe place that humans avoid, but near enough to people to teach her younglings how to hunt in a decade or two. She's picked the temple ruins as the perfect spot. But of course she doesn't want the Barony re-established. So she's gotten a tribe of kobold assassins to work for her, and she'll be trying to interfere with any hints of political stability in the region.
So I now have two major villains, each with a goal of seizing power, who will probably NOT want to work with each other, and a party of PCs. I have were-rats and a small dungeon. But the village is sort of "flat", and my PCs are still not strong enough to really battle were-rats, so I'm trying to add things to form emotional ties to the region, and to bump the PCs up a bit before they end up in a battle vs the weres... not always easy!