Personally, I like to use pre-made adventure modules. But I as a GM have always allowed the players to do what they want, rather than leading them by the nose or guiding them. You have less of an over-arcing plot for a given campaign, but the PCs get comfortable doing their own thing, and most eventually start engaging on side-projects that are essentially runs in and of themselves (magicians are very good at this).

Not saying I like being railroaded, exactly. But most of the GMs I have played with have put some thought into the backstory, and what's going on, etc. Because they have put time and effort into it, their pre-planned stuff tends to be more interesting, challenging and coherent than their off-the-cuff stuff. So I'm happy to stay with script, and if the GM wants to push the group in a certain direction, I'll go along, because there is usually something interesting down that way.

I don't believe in anything scripted in the sense that a PC has to be there for it.

I do everything on the fly.

I do not have "Main NPC's" There are many NPC's that the characters may interact with each with their own set goals and machinations during any given campaingn. If the players happen to cross over one of them, then I let the chips fall where they may. I peripherally keep track of the NPC's progress regardless of what the players do.

I do not script scenes in advance. I play out a scene dynamically. Since no NPC's are unkillable, scripting in advance is pretty pointless. If the PC's kill an NPC it was his own dumbass fault for putting himself in that position. Real mastermind type NPC's simply don't put themselves in that position on the first place.

Eventually when the campaign turns out to have a bad guy it's because the players chose to oppose him, or through the players actions he chose to oppose them. It's never decided in advance.

The same goes for PC's families relationships and contacts. I'll have fights with significant others, meeting new people outside of the actual "Running environment" and casual conversations with new people on their days off, the vast majority of which have no ulterior motive.

I create a world for the players to play in, and the story will find itself based on how the players handle their lives and relationships, both business and personal. The game is NOT about the Shadowrunning, the game is about the players lives, and Shadowrunning is what they happen to do for a living.

I generally just have some notes that I made up, though they may be very detailed, and NPCs made up. I like making maps if I have time too. I'd say about half of my stuff is scripted.
(I haven't posted here in almost 2 years. Holy crap.)