Be prepared for them to completely poleaxe your scenario. Players never quite do what you want, so be flexible. Think of the plot in broad sweeps, and ocassionally, if the players came up with a "plot" that you didn't, and it's better, run with it and call it your idea

Don't let them bully you though.
Reward stupidity with the kind of lessons that they will not forget in a hurry (by preference no fatal, but hey, if they're being really stupid...).
With B5, be prepared to take players aside (or pass notes) when the come across information the others might not necessarily know, and encourage them to do the same when appropriate.
Involve all the players. If need be, make up a "plot line" for the characters who are falling by the wayside, just so long as it "fits" and doesn't wreck the scenario.
Avoid going combat heavy in such a lethal environment.
Do have a sheet of names of major NPCs with a flow chart of their connections to one another, with room to pencil in the players' effects on those relationships.
If you come up with an NPC on the fly, keep a note of their name and some details so that if possible you can have him/her recur again in the future.
Don't be too clever (but that's not to say you can't be clever, just pitch at a level that you know at least one of the players will make the correct guess/connection). If the PCs can't work it out, you'll generally piss them off.
Remember what the limits of B5 technology are, and try to present your scenes knowing that. ie EA have rotational gravity generation, if at all in the main part, so make sure that the players are aware of the areas of zero-G that they will inevitably have to pass through.