Co-op is the major new selling point. Beyond that, the core formula hasn't changed too much, they've mostly just expanded on it with new characters, cards, enemies, etc.

But for anyone who's put a lot of time into the original, I think you'll really appreciate all the littler elements that really add up. They've had a lot of time to rethink some nitpicks with the original and learn some lessons from it.

For example, a lot of events in the first game were a binary choice of either taking something or taking nothing, in which case the event becomes an empty floor. Act 1 events in particular were often a trap. MegaCrit has talked about how StS2's events are being designed so that simply doing nothing is never an option, and I really really really like this! Just exploring all the new events is great, I'm suddenly prioritizing ?s on my paths just to see them all.

Boss relics have been replaced by a new system called Ancients. Part of me is still not sure how I feel about this, part of me is kind of excited by the fact that I don't know how to feel. The game feels very different without energy relics (mostly, there actually are a few but many runs will not see them), and that's definitely something that makes for a new and different challenge to get used to.

There's also a new mechanic where cards can receive Enchantments, either permanently or just for the duration of combat. You can come up with some very cool combos to experiment with using this system, and on the flipside the enemies that are able to negatively mess with your cards are super interesting to me.