I have a Dominion set that includes the base set plus Alchemy and Prosperity. The box contains a plastic insert with many slots of various sizes. I have stored the cards in alphabetical order mixing the three sets together, but this seems suboptimal. This probably has a really obvious answer, but is there a way to organize the cards so the plastic insert makes sense? Any recommendations?
There is a standard way to store those cards in the big box. Your big box should've come with a couple of large bookmark-shaped cards. One side has a bunch of card names upon decorative scrolls, like this:
photo from Board Game Barker
What you're supposed to do with this organiser card is to lay it down in the center of the box, between all the card slots. In the big box, that will look like this:
photo from the Board Game Geek page
If you put it down the right way, each card's name will sit directly beside a card slot. This organiser card will tell you which slot to put each card in. The thicker slots (e.g. the money slots) will have more corresponding spacing on the organiser card, so make sure those line up.
This organiser card also means I can check very easily where cards are: I can just look at the organiser, search for the name I'm after, and pull the cards out of the corresponding slot, which beats having to pull various piles out one by one trying to hunt for the right one. In the first photo, I can tell the Adventurer was put in that top left slot, the Bureaucrat beneath it, Cellar beneath that, etc.
The reverse side of the organiser card, with a bunch of blank scrolls, is for you to fill out if you ever come up with an alternative organisation scheme you'd like to use instead. (E.g. maybe you'd like to group all the attack cards together in the box, or something.)
The first thing I would do is leave out the Alchemy set. Beyond that I personally prefer alphabetical for the straightforward reason that it takes less time to dig out cards when you're setting up, and given that (after Possession) setup is the most annoying thing about playing Dominion this is pretty important.