Just finished Chapter 12 and did some post-game missions... I agree with a lot that's been said in this thread regarding the story and presentation. The basic concept and ideas of the story I like (I think the Ganglion's motivation makes sense and isn't terribly convoluted - which is a strong point for an RPG! - and the theme of humans freely mucking about with the natural order and creating beings to serve them is a good one and worth exploring).
The presentation definitely suffered with the way the game was structured, and I agree with earlier posters that in many ways this game felt experimental or like a really massive concept demo rather than a polished, finished product. I don't like it when games overexplain plot points and prefer it when they leave a bit of mystery (I thought one of Xenosaga 3's weaker points was that it was so explicit in its plot that you had to roll your eyes when everything was spelled out and you realized how silly the entire premise was), but here it went beyond being "mysterious" to just feeling "incomplete".
That being said - I sunk a ridiculous amount of time into this game, and thoroughly enjoyed it. Loved the customization options for the battle system, gear, and skells, even if the UI elements could have been handled much, much better. I loved that you're rewarded for customizing strong builds and thinking about how the various combat mechanics work together, and that even when you've maxed your level there are still enemies who can easily crush you unless you equip yourself well and stay on your toes.
I don't know if I necessarily need a direct sequel to this, and am kinda okay leaving Mira's mysteries unexplained (or maybe explained in other media, like a "Perfect Works" that showcases art concepts and story points) - but I'm definitely looking forward to whatever Monolith Soft puts out next.