I want to discuss a topic that hasn't really come up much, the evolving fluff of the Warhammer 40,000 universe. We've come along way from third edition when the stories were clearly all Imperial all the time. It was Guard crushing this and Space Marines kicking butt that. The Marcharian Crusade is the quintissential fluff event, and expansion of 1000 worlds, and the Heresy barely mentioned, Chaos was nothing more than an insidious menace (the concept of the "Long War" seemingly non-existant) and Abaddon beaten back in the Gothic War, Orks a beast to be eradicated and Tyranids a new threat to be dealt with. Then 4th edition came along and everything seemed a little more evenly matched. Tyranids were something to fear and took great sacrifices to beat, orks a Galactic Plauge, Necrons rising from the dark deep to strike unexpectantly, Chaos the main challenge to the rule of man as a constant threat and destabilizing factor, especailly with the 13th Black Crusade being a tactical draw but a strategic victory for chaos, and Tau a rising threat claiming unsuspecting worlds on man's ungaurded flank.
The the present age, 5th edition. It is the start of the Dark Times, the Imperium is stretched thinner than ever and beset on all side. In 5th edition the motto "There is only war" is embodied best. Even in game terms with expansions such as apocalypse support this. The Astronomican is weak and the days grow darker. The stage is set for an apocalypctic event. Even the BL books lead to this, with the Iron Warriors vs Ultramarines plots and Night Lords and Word Bearers series. 6th edition should be this event.
Mankind should be pushed to the brink, near what they were in the days of the Heresy and the time of Vandire. There should be great defeats and losses, with shinning beacons of heroism, sacrifice and defiance.
To me there are a few things that can do this in game and fluff
1- Primarchs- Well not loyal ones, but rather Daemon Primarchs for Apocalypse. This would also help reinvigorate Apocalypse I feel, as many people don't play it too much any more. They already did Angron some years ago in a WD (I have it someplace and need to find it). With the Horus Books growing in popularity, who wouldn't want to play with these veritable titans.
2- Abaddon gets past Cadia/Expansion of the 13th Black Crusade- This can even be supported with something not seen for a while- a summer campaign. Whether it gets to Terra or not is up to GW, but if you tie in some of the Blood Angel fluff surrounding Dante, this has a lot of potential.
3- Bring back another C'Tan- The outsider or void dragon would really mix things up and mess up humanity something good. The Void Dragon would be particularly good to coincide with a in game release of Codex: Ad Mech and open up the possibility for even more Apocalypse shenanigans
4- Eldrad Ulthuan is still alive- This guy is present at the darkest moment every time. If he comes back, we know something big is going to happen. Plus, this is a great tie in with number 3. Some Deceiver, Nightbringer and Harlequin goodness alongside in the fluff would be most excellent.
5- Another hive fleet- alot of potential here, for obvious reasons. You could though pit them against the Tau more and make a Imperium, Tau, Eldar trifecta of good. Same concepts can be applied to Ork Waaghs.
6- Just general mayhem. It is not longer the precusor of the end times. IT IS THE END TIMES. And some summer campaigns can really push this along. And then as 6th edition dies off, 7th edition can be a time of renewal again. Man can beat back the darkness and expand with crusades like Marcharius once again.
SO who else wants to see the galaxy burn? Hey, and 2012 is the PERFECT YEAR for world ending calamities to begin.