Well we know that Loki will be in the films. And I imagine that Nebula will be as well.
I really want to see the MCU delve deep into the character of Thanos. If the MCU has one weakness it's the villains. Now personally I feel that fans have far overemphasized the weakness of Marvel's villains...but there certainly are some examples of underdeveloped characters (Malekith, Whiplash, and Ronan). They CAN NOT let this happen to Thanos. If Thanos fails to deliver than the Infinity War will fail to deliver; and if the Infinity War fails to deliver so will the entire MCU. So a lot is at stake.
However the casting of Josh Brolin was an outstanding start. Also it appears that he will be making several appearances between films 6 (his introduction) and film 21 (his finale). Thirdly, Thanos from the comics is an amazingly deep and fascinating villain. He'd be very difficult to screw up on the big screen. Finally, I believe that Marvel is cognizant of this and they won't screw this up.