Thanos is most definitely the most talked-about villain in the Marvel Movie Universe, even though he has less than 30 seconds of screen time in a scene not even completely relevant to the story. People got to the point where they simply assumed he would be the villain to beat in Avengers 2... until the title Age of Ultron threw everyone a curveball.
Joss’ decision to have Thanos turn around, smile to the audience at the end of ‘Avengers’, it was always the plan to show that the Tesseract was indeed an infinity stone. A lot of that will tie first into ‘Guardians of The Galaxy’ which comes out next year and then where it goes from there we’ll see.
-Marvel Studios President Kevin Feige Interview on ScreenRant
But Thanos, according to Avengers director Joss Whedon, "is not out of the picture", which means he can still be part of the film, but obviously not as the main villain: perhaps more of a puppeteer like he did in Avengers, like Darth Sidious in Star Wars, or like he's confirmed doing in Guardians:
"Ronan the Accuser (Lee Pace) is very much the bad guy. And Thanos is lurking above it all. You will learn more about Thanos in Guardians, for sure. Certainly you’ll get more than the one turn-around-and-smirk. You’ll get much more than that."
-Kevin Feige Interview with Empire
Either way, Thanos is going to have another appearance in Guardians. He is so vital to the characters in the film that the movie couldn't follow the comics' actual story if he were absent from the film. Gamora has already revealed to be a villain at the start of the movie who turns good, which is a clear reference to her leaving her adoptive father's side... her adoptive father be Thanos.
Drax wouldn't even have powers if it weren't for the fact that his purpose is to destroy Thanos, hence the name "Drax the Destroyer". The way Kevin Feige talked about Thanos almost makes it sound like Ronan is just one of Thanos' little minions. Nebula, the bald blue girl seen in the trailer, is also thought to be Thanos's granddaughter. Even though Thanos may not be a major character, his role will definitely major.
We also learn that the average non-comic Marvel movie fan will soon learn what the infinity stones are, which is most definitely the biggest lead-in to the rumored Infinity Gauntlet story that will most likely take place in a Guardians of the Galaxy sequel, or Avengers 3. The Infinity Stones are 6 stones teased at the end of Thor: The Dark World that once united with the infinity gauntlet (seen below) gives the wielder unlimited power.
Ninety-nine percent of the film takes place on the other side of the universe with all new characters and all new worlds, although through certain connective tissue — such as Thanos in Avengers and some surprise appearances.
-Marvel Studios President Kevin Feige, Interview with SFX on upcoming "Guardians of the Galaxy"
So what exactly could this "1%" that isn't be? Well, this is all personal speculation here (backed up with facts), so just hear me out. The Gramosians, a unique alien race, are confirmed to be in the movie (as the director revealed Peter Quill is wanted for having sex with their duchess), and they have a rather important connection to Asgard: their leader Mercurio (possibly the duchess's father or husband) is a big enemy of Thor's. We also know if the Infinity Gauntlet story is going to go through, then the vault needs to raided somehow.
Imagine the ending scene of the movie: Mercurio reveals the Infinity Gauntlet and Tesseract's location to Thanos. Next we see Thanos busting open the doors to Odin's Vault in Asgard, sliding on the Infinity Gauntlet and balling his hand into a fist, and holding it up in bliss and disbelief and giving his infamous devilish smirk before letting out a disturbing laugh, which would actually be a rather famous pose for Thanos.