My two cents...
When I am running a long-term campaign, I generally start with a broad strokes outline of what I want to embody.
For this exercise, we are going to deal with Criminal syndicates in Seattle. (I'm partial to the Vory and Irish Mafia.)
Now we get to the story, at this stage we still want to be thinking broad strokes. So the Vory are going to start muscling in on established Mafia interests.
Enter the Players, what are their characters motivations? The first run or two can be on one side or the other, as you feel out the characters--do any of them have connections on one side of the fence or another? Are they trying to run by a code, out for the money, etc.?
Now we get into some of the grit, the Vory boss is actually trying to get control of the Mafia supply chain, to put a strangle hold on their smuggling and drug influences. Look at the puzzle from all the different angles and directions that you can find.
How are the runners going to respond to being hired by the Vory to beat up chip dealers and hijack shipments? Will they be upset about doing wetwork? Afterall they are only whores and addicts? But what if one of the prostitutes is a friend of a friend?
Just keep adding on layers and watch for the players, they have a pesky habit of starting their own sidequests and crusades.
For a PbP Mission, I generally start out with a storyline that's slightly more filled in.
We'll use
Chasing the Prize as an example. This game was designed to be a legitimate bounty hunt.
I made the bad guy a virologist who skipped bail--but what's interesting about that? Let's add some depth to this guy...He's researching a cure for VITAS, the plague of the modern era. His research is primarily looking at cannibals in the West Indies who seem to be immune to the virus (my own tidbit) and victims of the Krieger strain (ghouls). So our good doctor, need a name--Lucien Ballefour, was running a street clinic to help out his fellow man and perform some heinous experiments on the sly. He contracts HMHVV and tries to hide the fact from the people at his research lab. (Otherwise he'd have to explain what happened...)
So now we have a ghoul running loose, he's intelligent, educated and more than a little scared. We can add environmental complications like a viral weapon (VITAS anyone?) being released in the subway during rush hour; humanitarian aid from Ballefour Pharmaceuticals as they offer free innoculations of their VITAS cure which is still in clinical tests; and foreign travel--Lucien has dual-citizenship.
Now all we need is to grab a group of players who want to play legitimate bounty hunters and we are ready to go.