I hate the interface. That's about it.
For those who say 'it's more like IRL Dominion,' I agree. But IRL Dominion is the inferior version of the game. And for those who say 'it's more appealing to the common fan,' I'm not sure I agree. But regardless, I'm not the common fan, and I happen to hate it.
I can't really imagine spending money to play it that way, even with Dominion being my favorite game. We'll see if that changes once Iso finally goes, but...to me it's just a completely different (and far worse) game.
I find it hilarious that you find what is essentially bug-testing software to be superior to an actual finished product.
What's so hilarious about it? My GF and I will hang out, we will both be right there, with all IRL dominion expansions, and yet usually choose to just play against each other on isotropic as opposed to with real cards. Why? There's no time spent taking out all the cards or putting them back. There's no time spent shuffling. There's far less downtime. When we play with Dark Ages now and I've successfully built an engine and she hasn't (or vice versa) and her turns are 5 seconds and my turns are 90 seconds every time, it gets boring for the other person. That doesn't happen to nearly the same extent online.
Dominion is especially the type of game that works well online, for many reasons, but two of the main ones are:
1) It has a lot of downtime IRL
2) Not every game is particularly interesting. IRL, if you have a game that ends up being uninteresting, you can either just quit in the middle or spend the next 20 - 40 minutes playing it through. Online, you get through the boring game in 5 - 10 minutes.
I much prefer playing online to playing with real cards (though I like playing with real cards too) and I don't really understand why that's funny.