I think the main issue with the game in its current state is that it has an inverted difficulty curve : at first it is very difficult and you rely mostly on luck, if you are able to deal with enemies it is great, but you are often stuck with enemies that you can't kill because there is no available match nearby. Rats are especially deadly in early games because they are really fast and decrease your max HP, so even if you get a healing skill such as "tap the source" it becomes useless. However, when you survive the early game and manage to have a nice build you become unstoppable.
What will be a pain to balance now is that shuffling tiles became a necessity to survive because of the grey tiles, but in the end even with the miner skill once I started a combo I would clear the board.
Maybe putting a limit on the max HP could also help ? (As you can see in the screenshot, half my screen was filled with hearts, even if I picked offensive skills most of the time) I also had so much vampire touch that killing any enemy would instantly heal me completely. (not that it mattered at that point because I would clear the board almost every time) so maybe put a limit on the healing skills too.
Skills that deal damages, like poison trap and bows don't have a limit either, so after a while most enemies would die as soon as they moved xD
The second best skill in the game is "Good learner", because twice as many skills means that you get to completely overpowered combinations twice as fast, (careful study is pretty powerful for the same reason) and when you can reroll the skills a few times for each because of a few "gambler" it is really easy to break the game. However, the most game-breaking one is by far "Chaos", because it randomizes the color of skills : with this, any tile can one-shot enemies with a lot of poison, you can fully heal when stepping on any color, etc... It is one of my favorites because it makes most of the other skills more interesting, but it also completely breaks the game's balance at the moment.
As for the score issue, the "patience" skill plays a big part in it, because I could just double my score again and again hundreds of times and it grews exponentially, so maybe replacing it with a fixed amount of points would be a bit better to prevent extreme scores.