I do play on goko, but mostly adventures/vs bots. I keep meaning to start playing vs people, but never really get around to it.
Lack of matchmaking mostly. I want a single "find me a game" click, and hopefully to find one matched to me by skill, so I'm not beating up on newbs (or stressing out about losing ranking if a newb opens Mountebank/Chapel on me). And so I don't have to create a game and wait for someone to join. I want
1) An automatch
2) preferably, an automatch that automatically looks for somebody close to you in ranking.
Missing cards isn't an issue anymore - as someone pointed out recently, Goko now has as many cards as Isotropic does. (Missing 2/3 of hinterlands and alchemy, whereas Iso is missing Dark Ages, which is huge. And I like Dark Ages more than Hinterlands and Alchemy anyway.) I did recently buy all the goko sets.
Also, my last memory of playing-someone-on-Goko was playing a few games with someone a bit back and having it freeze on me. That just kills interest. I think they've fixed that particular freezing bug (it was with Watchtower) but the bug reports tell me there are other ones which crop up. Yeah, it's a beta, it's ok, but still, it doesn't fill me with a desire to start playing lots of games vs humans if they'll randomly crash on me. It's ok against a computer, I just refresh and try again... but it is true that basically whenever I play the campaigns, the day will end with some sort of crash or freeze or game-becomes-slow and I'll be like okay, I guess that's my signal to stop Dominioning for the moment.
Oh, and it gets slower after a bunch games on firefox... they say it's better in firefox 18 beta, but I'm not installing a new web browser manually for them, especially not a beta. I'm lazy, I'll wind up on firefox 18 when ubuntu automatically upgrades me, probably a bit after it leaves beta :/