When Joss Whedon was asked how he would approach Avengers 2, he responded with “By not trying to go bigger. By being smaller. More personal, more painful." (1) This leads me to believe that it has to do with villains from their past films. Let's take a look at who that might include:
During a recent twitter Q&A, Kevin Feige was asked "Will we see Extremis again after IM3?" and his response was "Yes." (2) Keep in mind that we never see Killian's body at the end of IM3 (or Savin's, either). As for Thor, maybe Malekith lives or perhaps the Enchantress or Executioner is mentioned/cameoed in TDW.
During a radio interview, the host asked Frank Grillo if he was "making more Crossbones appearances after Captain America: The Winter Soldier, to which Frank modestly confirmed. “Yeah, it's a good run,” Frank Grillo said." (3) And maybe Robert Redford's character in CA: TWS will actually be Baron Zemo or perhaps Thanos rescues the Red Skull from the dimension he was sent at the end of TFA.
In the Marvel one-shot The Consultant, Agents Coulson and Sitwell discuss the fact that the Abomination survived and is in SHIELD custody and that the World Security Council wanted him released in order to join the Avengers Initiative. So we know Blonsky is alive and there is a rumor that SHIELD's actual HQ, Triskelion, will be featured in CA 2 and this base is the location of a super-villain prison in the Ultimate comic universe. (4)
I'm guessing that Thanos' back story is fleshed out a little in Guardians of the Galaxy (who he likely defeats and/or kills to heighten the stakes and highlight how dangerous he is) then he rounds up these villains to take on the Avengers, similiar to his approach using Loki but with his idea being that this time, these villains know all our heroes weaknesses. They would, of course, be defeated and this would make Thanos the puppet master of the trilogy and set the stage for the final showdown in Avengers 3, after he presumably acquires the Infinity Gauntlet (which would just make him too powerful in the MCU) or the Tessaract (which could make a bookend on the trilogy since we've yet to see it's true power). When Whedon was recently asked about Thanos, his response was “Thanos is more powerful. He’s not someone you just trot out and punch him. Like you did in the comics, you want him to be threading through the universe and to save the big finale for the big finale." (5)
1.) http://screenrant.com/avengers-2-story-joss-whedon-kofi-158346/
2.) http://www.slashfilm.com/kevin-feige-answers-iron-man-3-burning-questions-teases-marvel-cinematic-universe-links/
3.) http://www.comicbookmovie.com/fansites/MarvelFreshman/news/?a=69509
4.) http://www.comicbookmovie.com/fansites/TheDailySuperHero/news/?a=82213
5.) http://screenrant.com/the-avengers-3-thanos-joss-whedon/
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