One of Justin Roiland's ideas when turning Rick and Morty into a show, was to end every episode with the earth getting destroyed due to their adventures. He wanted it as a statement that he didn't care about continuity. When discussing the idea with others it got turned down, since the joke would become dull really quick.
The simulation episode is some what inspired of a really bad drug trip that one of Roiland's friends had. He apparently questioned reality and thought the "invaders" were after him. He laid down naked on the floor, thinking he was invisible as long he didn't wear any clothes (hence why Rick and Morty strips off their clothes in the episode).
Dan Harmon and Justin Roiland really didn't want to attend a big convention after a hangover. Their friend convinced them to go, claiming that their fans won't care how they act: "You guys can seriously just go in there, flip them off and leave and their lives will be completed." They went there, flipped the audience off while saying "This means we love you guys. This is our way of showing you our love and respect." The audience loved it. There's a slight representation of this moment in the episode "The Ricks Must Be Crazy" from season two.
Dan Harmon really hated the sound of Mr. Meeseek's voice at first. "When me and Justin were trying ideas with each other early on, we would sometimes get stuck. Like, nothing would come to us. While I'm there trying to think what should happen next, he would make this fucking voice... 'I'M MR. HARMON, LOOK AT ME!' I would ask him if he could knock the shit off. 'CAAAN DOOO!' he'd reply. It was like a nightmare, I hated it. He then tells me he will make a character using this voice. The fucking idiot."
One of the show's writers has claimed that he's planning a really dark twist to the show in an upcoming episode: "There won't be a joke or punchline in it. Not even witty one liners. It'll be a more story driven with a lot more drama. It's going to have a very different tone than the other episodes."
"Time to get Schwifty" is a song Justin Roiland wrote and recorded with some friends as a kid. Roiland had a passion for music when growing up. "When I let some friends listen to the song the response was 'It's pretty good, but it's not anything special.' So, now I've put the song in the context where it saves the world. Suck it, Carl!"