If you haven't yet come across the Atlas of Mystara, by +Thorfinn Tait and the excellent efforts made with regards to mapping Karameikos, it is time to correct that. That map is going to be very useful in the days ahead. While I would prefer a map six mile hexes, it is by far the best map available to me.
Between the newbies guide at Pandius and GAZ1 The Grand Duchy of Karameikos being available on drive thru RPG, there is a good amount of information of the setting out there. Perhaps, that is the wrong way to put it. What information is out their, while very limited is, very easy to read. While there is not a lot of information on Karameikos, that which there is, is singularly accessible. GAZ 1 may not be a long book, but I have a clearer idea of what Karameikos is like than any area of the forgotten realms I have learned about through the 3.5 campaign setting. The writing is simple and beautifully clear.
Thanks In search of Adventure, a fair amount of the material from the B- Series is set in the Grand Duchy, which means Keep on the Borderlands and Caldwell Castle and beyond are on the table with some ease. Add to this the fact that King's festival and Queen's Harvest, were written to be set in the grand duchy. It is also a location that could conceivably play host to the three DnD adventures which most shaped my early life, Escape for Zanzer's dungeon, Assault on raven's Ruin and Quest for the Silver Sword. All three are adventures I wish to include in my up coming campaign.
What is lacking, is a way to tie this material together, into a wider campaign that amounts to something more than a collection of things that happen one after another. While I wish the campaign to generate its own emergent narrative, as something of a sand box, I have no interest in just seeding the campaign world solely with purely independent and self contained adventures with no connection to one another. Better a mixture. Some adventures that are nothing more than isolated events, some that occur because of trends, and other that are tied to one another.
As a result, I have plans for two plot lines and a general trend. These are still in the earliest stages of development, but I thought you might find them interesting. It is possible that, as I read In search of Adventure, I might steal some connective tissue from there as well.
Plot 1: The conspiracy.
A group(possibly the Veiled society) is attempting to destabilize the duchy to grab a wider share of power in the young nation. Several adventures show some sign of the group being responsibility for the troubles the PCs a thwarting.
Plot 2: A crypt to call home.
One of the grand Duchy's Vampires has set out to establish a new lair. The PCs are one of the tools they are using to achieve it. Initially having them clear out the location of its new lair, and then setting them to various tasks that, without their knowledge, helps to secure the location.
Trend: Humanoid threat.
Up in the black mountains, all manner of humanoid clans are gathering and swelling into a force that could well sweep down into the grand duchy.