The two biggest changes for me are the new targeting system, and the ability to repeat synths on local levequests. You can now choose specifically what you want to target; party, enemies, etc. And there's a hell of a lot less button mashing when crafting now.

They also added "mini quests" recently, and although lackluster, they're still new and offer something else to do.

I guess the biggest change of all would be the among the devs. I'm not sure if the OP knows or not, but almost all the top dogs on the production staff were fired/quit in December. The new team is MUCH more sociable and the director, "Yoshi P" as he is known, has been very forthright with information about upcoming patches and whatnot.

Oh and yes, the fatigue system still exists.