Are there any actual mechanical and game play differences that are significant enough for this game to be considered anything more than a re-theming of Cosmic?

I wouldn't even dream of throwing money away just to have a 2nd copy of Cosmic with a different theme slapped on it, it would still be a second copy of Cosmic.

However if there are significant mechanical and game play changes I may take a closer look at this...

FFG is on a kick right now of slimming down and streamlining a lot of their games and I imagine that's what's going to happen here.

Same game with a more popular theme, with the mechanics just parsed down a little and eveything just tightened up a bit.

Based on the preview article( https://www.fantasyflightgames.com/en/news/2016/7/22/the-iron-throne/ ), the main difference seems to be each house gets 10 unique cards for their "House Deck" in addition to their Leader's Power (equivalent of Alien Power).

Now, this could mean either that you start with 10 unique cards that get expended somehow, or that you only get those 10 cards (rather than drawing from a single pile like in CE). Or it may be a combination of a center pile and refillable unique cards?

Hard to say. Personally I'd be intrigued if they went the route of each player having a smaller, known card pool, as that would cut down on the RNG and make the game more strategic than its predecessor.