The game will not have a supernatural twist
The first three games in the anthology (as well as Until Dawn and The Quarry) have all had supernatural twists. Maybe this one will buck the trend, seeing as how it's based around a Serial Killer with a twisted ideology, à la Saw.- Confirmed, since it isn't part of the twist, though whether Du'Met is supernatural or not is subject to debate.
The Devil In Me will have Adjustable Censorship in some capacity
Because the game won't just be Bloodier and Gorier, it will be so bloody and gory that there will be an option to censor the most extreme scenes of violence and gore, in a similar vein to Martha Is Dead.- Jossed.
Countering the above WMG, if there is a supernatural twist, it will be...
The Serial Killer (Granthem Du'Met) is being possessed by Manny Sherman. After Sherman was executed for his crimes, his spirt possessed his mentee, who created an animatronic out of Sherman's corpse, so that he could continue his work from beyond the grave.- Jossed.
The title isn't just a shout out to H. H. Holmes, but very literal.
As it it will turn out the serial killer in the game is either possessed by the Devil, or by his "mentor" looking to finish his life's work, which, to build upon, is to summon Satan.- Jossed, at least in regards to Du'Met desiring to summon Satan. Jury's still out on whether or not Du'Met is possessed by, or host to, some sort of supernatural entity.
There will be one hell of a Downer Ending where Du'Met succeeds
Du'Met's goal, according to the description on the Dark Pictures wiki, is to become the most successful Serial Killer in history, even keeping a Kill Tally. The trailers show multiple traps where we have to save various people and, given the nature of the game, we will have the opportunity to not save them (either by failing the minigames or quick-time events or just walking straight past them while they beg for help). The worst ending would be triggered if none of the potential victims were saved and all five protagonists were killed by Du'Met, either through a Death Trap or directly (or possibly even through those animatronics he created). If everybody that can die is killed by Du'Met, he will have succeeded in killing more people than any other serial killer, thereby "winning".- Confirmed. See the Ultimatum ending.
Du'Met will be killed by a Death Trap himself
If all five protagonists survive and they rescue enough people, they will team up, ambush Du'Met, and knock him out. While the guy's unconscious, the characters will build a Death Trap of their own using their unique skills and equipment found throughout the hotel, then Du'Met will be put into the trap before he comes to. If the trap is put together properly, Du'Met will be killed by it, while all the people he tried to kill over the course of the game watch him.- Jossed. He always survives.
The main characters are descendants or related to victims of H. H. Holmes
Du'Met is trying to copy H.H. Holmes, and the main cast are the perfect victims because they're all related to the original victims, so he can recreate the original crimes again.- Jossed.
Du'Met is either a humanoid drone or a self-made cyborg
The constant use of animatronics throughout his Murder Castle, as well as his notes on integrating them into organic tissue offers up the possibility that there's a technological reason behind his superhuman durability and resistance to pain.