Personally I decide on what expansions to use and then laboriously go through each deck separating out the expansions I'm not using and put them back in the box. I always leave in the base and I leave in the Miskatonic cards that match the combination of expansions I'm using.

I know CotDP has optional rules for separating out the base cards and just using CotDP. But I've never done that.

Are there any other variants that people use?

Everything mixed in all the time. Item, Skill, Spell decks are always "active", Location encounters are all "active" except when a required expansion (usually Black Goat for Cult encounters) is not currently "in play", Other World encounters are always "active" and the Mythos deck works by checking first for expansion symbols in the corner. If all expansions pictured are in play, the card is valid, otherwise its discarded and another is drawn. I think it's less time consuming than separating everything, everytime, and it lets you decide what expansions to play even 10 seconds before starting to actually play.

I tried separating during play but around the time I got all the expansions I found it too distracting during game play.

I stumbled across Tibs' BBG post about mixing CotDP original and revised. Any other stuff like that?