So I had been waiting for my first payout for a while, so I contacted support and they quickly got back and said the reason was there was a number of instances of scrambled e-mail addresses who had bought it and that had to be investigated.
Which I completely understand, I checked the list of buys and there was a whole series of seemingly randomly generated emails and names there. So I'll just wait, I'm in no hurry and it's a tiny amount of money.

BUT my question is... What is the point of this, and is there anything I can do to prevent this in the future?
Like, what do these weird purchases gain by buying my little random game? Apparently none of them had downloaded it either. So what's the scam here? o_o
And before initiating the payout, could I have done something to manually deny/refund/exclude them?

Unfortunately, sometimes fraudsters will target random game pages on itch.io to test stolen payment information.

There’s not much you personally can do about it. You’ll have to wait for our team to review the transactions and process refunds and notify the payment processors of fraud. If you see suspicious transactions, you can always send a support ticket to our team so we can start processing those transactions before you even request a payout to avoid any delays when you do eventually request a payout.

Hope that helps