So, now that the casting for Thanos seems to have been announced and we can start thinking of the Mad Titan as a more concrete, tangible presence in the MCU... let's talk about how you go about portraying him.
I've loved Thanos since I was a kid, going back to his various cartoon/video game appearances and some occurrences of him showing up in comics back at that time.... though it's only been over the past couple of years that I've read some of the Jim Starlin stuff and come to fully appreciate the character's awesomeness. For me, Thanos is THE Marvel Universe villain. Bigger than Doom, Magneto, Red Skull, any of them. He's the Biggest of Big Bads. And with the direction the shared universe of the films seems to be taking, especially with Doom and Magneto owned by Fox and Loki shifting into anti-hero territory, Thanos is clearly being set up as THE overarching villain of the whole MCU too. What do Marvel do to make him special?
Loki is, of course, excellent. He was already another of my favourite comic villains, and Tom Hiddleston must be commended for extending his popularity to a whole new demographic of fans. But he's so charismatic that one is left wondering what MCU's other villains can do to stand out from the crowd. Then you consider that Age of Ultron is likely going to give us in Ultron a heavy-hitter who can take on the whole of the Avengers by himself, so that angle won't even be new.
Perhaps the key is to underscore just how evil he is. Truly emphasize how horrifying in scope and brutality his plans and ambitions are, to make us frightened of him ever getting enough power to realise those goals. Really emphasize his Machiavellian qualities, too. Some cues could be taken from recent TV villains like Mads Mikkelson's Hannibal Lecter or Billy Bob Thornton's Lorne Malvo from Fargo - primal forces of evil who cause great pain to others or manipulate them into doing terrible things apparently for their own amusement, and/or as microscopic cogs in a massively complex agenda that it's impossible to make out in full from the close angle we're looking at it in the moment.