Firefly / Serenity. The occasional mini-series that Dark Horse's Scott Allie hopes for, and the "fill-in-the-blanks" mini-series we've already had set in between the series and movie, simply aren't enough for me. Since we'll never get a new television series flying, I'd love to have a new series exploring how the revelations in Serenity will affect the 'verse and the roles that Mal, Zoe, etc. will play in events. I like to imagine a new Browncoat uprising...
Failing that, I'd like to echo Theonethatis and say Crusade. Perhaps it could start with some of the finished-but-unproduced scripts. I'd want it to, like JMS originally intended, follow the "find a cure" plotline for a year or two, then move onto to the lingering Shadow influence within EarthGov and Excalibur going rogue. I've enjoyed JMS's original comics work far more than what I've read of his contributions to licensed superhero material, so it really seems only natural -- and a big-time missed opportunity -- for Crusade not to have a comics continuation.