I'm guessing that a lot of these are already taken care of, but I'll list them for the sake of completeness:
1. Always make the entire card name in your hand readable. The number of times I've had a big hand in MF and have had to identify my hand by the top-left corner of the card art is silly. I assume this was done on day one of the new client.
2. Disambiguate the card-selection actions better. The MF colored borders aren't enough, as has been pointed out many times, and the plus sign on the pile selection even when not gaining is terrible UI design.
3. Allow undo for non-information-providing actions. I allow this in IRL games. For example, if you play a terminal draw card, then realize you didn't play a village first, there's no undoing, because you have looked at the cards that you drew, which provides information you didn't have before making the "error." However, if you trash a card, then change your mind, you should be able to pick it back up and trash a different one, or even rewind the trasher action to your hand (as long as it isn't something like Junk Dealer or Lookout, which draw or reveal cards.)
The implementation of this wouldn't be too difficult: Keep a list of the information-providing occurences that can occur in a game of Dominion and use those as stop points beyond which the undo command is not permitted to rewind. Playing actions or treasure cards from hand is not inherently information-providing (information given to your opponent would not count.) Going from action to treasure phase is not inherently information-providing. Trashing cards is not inherently information-providing. Gaining cards is not information-providing, except for gains from a randomized pile (Knights.) Drawing cards or revealing cards from your own or your opponents' decks is information providing, and should place a stop point. "Look through your discard pile" actions are information-providing.
A well-implemented undo can make up for a ton of misclick-creating UI problems that users are almost certain to complain about, no matter how good your design!
4. An API for developers
Ok, this might sound like pie-in-the-sky, but hear me out. I'm a software developer for a living, so I know that developing user interfaces for new features is often the most difficult part of the development process. Often more difficult that the feature itself. However, exposing some of the internals for tweaking by other developers is relatively easy. If you're using any sort of internal scripting language, it would be great to expose that for hobbyists. Failing that, allowing some sort of plugin system would be great. Here are some things that I would love to be able to experiment with:
-- creating custom bots, both for pre-constructed and random kingdoms
-- a "bot league" where bot matches could be set up (and play something like 100 games against each other almost instantly for a good statistical sample.)
-- custom kingdom creation rules
-- custom campaign creation, including bot setup, starting conditions and rule variants like MF. MF's campaigns seriously lack imagination and I'm guessing a lot of users could do better.
-- custom kingdom setup rules (my IRL group plays with 4 Provinces/Colonies per player for up to 6 players.)
-- custom hybrid cards
That last one is a bit tricky. Note that I didn't just say custom cards. Some users have asked for the ability to create user-designed cards, but that opens too many cans of worms. However, the ability to create cards that are simply a variation on existing mechanics, using the already-present code modularly, would be an interesting thing. For example, people have asked, what would a card that did +1 card, +1 action and nothing else cost? $0? $1? Usually skippable, but could be huge in the right Kingdom. What about cantrip-money that came with two Coppers? What about a vanilla terminal $3 +buy?
Sure, none of that is "real Dominion" but just look at the incredible amount of discussion this game has created in this forum. The puzzle section has some truly astounding stuff in it that will never happen in a real game, but what if someone turned some of those puzzles into campaign stages that were actually playable (with achievements; perhaps even mandatory ones, making the puzzle an integral part of the gameplay!) The variant card forum is interesting, as it usually produces dramatically overpowered (and sometimes underpowered) cards, but the ability to playtest those online would be great.
Expose an API, and it allows for an explosion of creativity among the developer-player community. I'm not sure how bit that community is, but I think it's worth considering.