Advancing the Plot: In the 65th millennium, there is only war.
My own idea for advancing the plot. I limited myself to some simple rules to help the transition, which are below.
#1: Something had to give: There was only so long that the Imperium could remain in a state of erosion and decay before being reborn entirely or simply imploding and utterly ceasing to exist at all. In this time-line, it has rebirthed. This is truly a "Rebirth" in the essence that things have changed. The Imperium is not as it was, and some of it's central characteristics have intrinsically molted and metamorphosed into something entirely new. In response to this change, every other faction shifted as well, and you'll see why. If you want everything to stay the same, then I suggest a reboot of the entire 40K universe.
#2: No faction get's to claim moral superiority, they are egalitarian in their Grimdarkness: The Tau got a lot of flak because they weren't thriving on Grimdark. The argument goes something along the lines of "There should be no central protagonist in 40K. They all had their merits and they all had their fallacies." In this way, many people thought that the Tau stole the spotlight, because they didn't seem to have any sort of moral flaw in their character, instead seeming to be a bunch of peachy Mary Sues (to be fair, the Ultramarines of Macragge could have fit under this banner as well). I like this line of reasoning. There has always been "Only War" in the 40K universe is because each faction draws a hard line around some central tenant that they will NEVER compromise over. In this way, all factions are mutually exclusive and cannot coexist with the others.
#3: They're still "Your Guys" Your guys are your guys. You set their idiosyncrasies, their histories, and how/why they came to their current conclusions. The reason I gave two and a half millennium between 40K and this new setting is because it gives a lot of time to fill in the blank and gives a lot of wiggle room for things to get as they are now. In the interposing time between then and now, heroes have risen and fallen and countless legacies have been born and lost.
So here's the first faction: the New Imperium of Man.
A New God Rises, and an Old Ideal Dies: The Transformation of the Imperium
The Emperor of mankind is either Ascended or has achieved total martyrdom, depending on who you ask. In the 52nd millennium, a Warp Storm consumed Holy Terra entirely, and gave rise to a new Chaos God of Merit, Justice, and Stability. His Followers call him "The Emperor Ascendant, the Omnissiah."
He claims he is the Star Child, come again. But his ideals are not as they were. He claims he has grown. He says that objective truth is impossible, and that faith is now a central tenant for all creatures. This is the New Emperor of Mankind.
Many humans call him The Imposter, The False Idol, The Antithesis of Truth, for he has clearly abandoned the Imperial Truth as it was known, and embraced the Imperial Creed instead. To them, this clearly is not the Emperor. For them, it is easier to accept that the Emperor is truly dead, and that this is merely an unseemly mockery of everything that he was.
Which side is right? The Creed or the Truth? Neither? Both? Nobody can know for sure. It is unlikely even the New Emperor knows the answer.
This Emperor, if he is indeed the Emperor, is more tolerant...and yet more frightening. His demands are as follows:
#1: All sentient life is to bow before the Throne, or be destroyed.
#2: All sentient life is to be bound by the same code of conduct, the same tenants of justice, the same ideals of enlightenment.
#3: All sentient life will rise on their own strength, or fail in their inadequacies. There shall be no mercy, only merit.
#4: For every being; a place. For every tool; a purpose. Everyone contributes to the Imperium if they are to be a part of it. And all things are to be a part of the Imperium, given time. Even the other four chaos gods are to be shackled at the foot of the Golden Throne, eventually.
In its own way, the imperium is admirable in it's inclusive nature. On the other hand, it is horrifying in it's need to assimilate all other life in the galaxy.
Those in the Ecclesiarchy adapted to this new development with alacrity. Indeed, it was the Ecclesiarchy who is primarily responsible for this new Chaos God.
The Brotherhood of Mars seems the same, but on the inside, everything has changed. All souls given in the Emperors service are sent to the Soul Forges of Mars, where they are remade into wargear. Every Lasgun, every Bolter, every single munition from the greatest Battleship to the smallest autogun, is made of souls given voluntarily for a new lease on life, in service to the Emperor. When an imperial Guardsmen mutters the Litany of Reloading, there is a soul listening, grateful for the continued recognition of meritorious service, grateful that those still living who honor his or her memory.
The Imperial Guard has been transformed into the Imperial Army once again. But the Adeptus Astartes are now grown from the common guardsman based not on Genestock or science, but based on how much they have given for the Imperium. Indeed, the Imperial Guardsman is the the building block from which all other agents of the Imperium draw heritage. The longer a guardsmen has fought, the faster, smarter, and stronger he becomes. This may manifest itself in a variety of ways. A guardsman might find himself slowly morphing into a shocktrooper, and then from a shocktrooper into a neophyte battle brother, from a neophyte into a full fledged space marine, then into a devestator and so on. Or he might find himself transforming into an elite sniper, and from a sniper into a terrifying vindicari assassin, and from a vindicaro into an Imperial Knight equipped with a long-range cannon.
A guardsman and his wargear are inseparable, from life until death. And they grow in merit together. The piece of flak armor will eventually evolve into carapace armor. The Lightning Fighter will metamorphose into the Thunderbolt, and from a Thunderbolt into a Marauder. These are the Emperors gifts. And thus the pilots of Titans, Cruisers, and Landraiders are truly terrifying to behold, for these are pilots that have seen centuries of conflicts pass them by.
The Inquisition still exists, for it is the guard against Apostasy. All residents of the Imperium know that the Four Chaos Gods are to serve the Emperor, not the other way around. None of these four entities are a truth unto themselves, they are merely raw elements of the warp that are acting as immature and unruly children against the true master, which is the Emperor.
Nurgle shall eventually know his place as a force of benevolent rebirth and content, not as a belligerent of stagnancy and death. Khorne shall know his place of Chivalry and Honor, not as a howling rampage of death and destruction. Tzeentch shall know his place of progress and improvement, not as the shadowy puppet master engineering backstabs and trickery. And Slannesh shall see his place as a pain reprimanding those who act of selfish gains, and a pleasure for serving the Emperor and the Imperium of mankind.
Continued existence of Man Outside the Imperium:
There are humans (and space marine chapters) who still hold to the Imperial Truth. But they have been forced to abandoned the techpriests of mars and the ideal of a still-living Emperor. To them, the Emperor died upon the Golden Throne as a Glorious Martyr, fighting for objective truth until his dying breath. No longer do they wear Ceramite Armor or wield the holy bolter, long celebrated instruments of man's glorious crusade against ignorance. They have been forced to borrow foul xenotech, from the Plasma Guns of the Tau to the Guass Rifles of the Necrons. These reverse-engineered instruments are, of course, modeled in in the classic image of the imperial tools of old. But at their heart, these are still items of the foul xenos, shameful proof of how the ideals of humanity have been brought low.