In House of M, the authors introduce Layla Miller, a young girl who is able to make characters remember that they are in fact part of a Cosmic Retcon by Scarlet Witch. After the event, she disappears for a bit before reappearing in X-Factor, where it is eventually revealed that she has the power to bring things back to life, only without a soul. Now, if you'll pardon a bit of Wild Mass Guessing, here's where the brilliance kicks in: everyone in House of M was dead except for the Scarlet Witch, who had killed everyone. Layla brought the people back to life, and they lost their souls in the process. For example, Spider-Man sells his marriage (but not his soul) to Mephisto in One More Day; Cyclops starts X-Force, a black ops team that goes against the peaceful co-existence that the X-Men have gone for in the past; Emma Frost uses a Deadly Game to select students who will have continued education following the Decimation; Hawkeye decides to just outright murder Norman Osborn after he becomes head of S.H.I.E.L.D. replacement H.A.M.M.E.R.; and Doctor Strange starts using darker magic. Whilst it doesn't apply to everyone (Luke Cage, Iron Fist & Ms Marvel, for example) a number of the characters who had their memories restored by Layla have been subject to some sort of derailment since House of M.
Avengers Annual (2012) offered the possibility that the Marvel universe after House of M isn't actually (or ultimately) real, just reality as Wanda created it in her madness. This could be Fridge Horror or Fridge Brilliance, depending on your perspective — all the character derailment of the last few years is due to the characters not being their real selves, but the people as Wanda imagines them to be.
When mentioning the Decimation, people usually snark that over 90% of mutants lost their powers, yet somehow almost none of the big names (Cyclops, Wolverine, etc.) were effected. Obviously, this is because Marvel couldn't just spontaneously de-power some of their biggest names, but if you think about it, there might be an in-universe explanation. On some level, Wanda must be aware that some mutants would be miserable without their abilities - especially those she knows, and has interacted with. She removes the abilities of thousands of mutants she's never met, and herself and her family (presumably because she thinks Pietro would be better off and wants to punish her father), but when it comes to the X-Men? Subconsciously, despite her madness and misery, she can't go through with it, and the effect is sporadic at best.
Spider-Woman questions if it's not best to leave the effects of Wanda's reality warp in place. It was revealed several years later in Secret Invasion that Jessica Drew had been replaced by a Skrull impostor before she joined the New Avengers & when she regains her memories of the original timeline, she doesn't blurt out "Holy crap, the last thing I remember was the Skrulls kidnapping me!" - "Jessica Drew" in the House of M timeline is Veranke, whose greatest desire was for the the restoration of the Skrull Empire.
This one was intentional. Per Word of God, Secret Invasion had been being planned since at least the beggining of the "New Avengers" comic book. The authors intentionally left several Chekhov's Guns around, for the time when the reveal was made and the fandom had to begin the big guessing of who was or wasn't a Skrull.
When Layla restores someone's memory of the real timeline, they have to go through everything in seconds. In Spider-Man's case, that means the deaths of Uncle Ben & Gwen Stacy. For Emma Frost, that means the genocide of millions of mutants on Genosha. For Hawkeye, this means knowing that both he & the woman he loves are supposed to be dead.