It's not exactly a radical departure from the timeline, but I'm having a lot of fun running act 1 of my campaign in the early 2250's, about 5 years before the start of the series. The Centauri are decadent, depressed and weak, the Narn are vicious and manipulative, the Minbari are barely to be seen, and Earth is trying to rebuild after a nearly-genocidal war. The tone is Babylon 5, but a little more dark and desperate than the actual series. (well the first couple of seasons anyway)