I am in the process of mixing all expansions altogether and keep it this way (BGG files has nice tuckboxes to keep all material in neat boxes), but am aware and concerned by the "dilution" problem. For people who have done this, do you play sometimes specific combos, by simply ignoring cards that contain symbols of an unwanted expansion ? I am wondering, is this practicable ? Or do you prefer removeing the cards before play (but that must take ages !) Thanks in advance for your opinions.

As soon as I got Black Goat, I started randomizing all my expansion combinations. This was kind of neat, but I eventually just itched to mix them ALL and ALWAYS play with them all mixed (that is, 5-expansion games)

However, when I used to pick and choose combos, I would merely ignore cards with expansion symbols not used in the game and continue drawing.

These were the only drawbacks:
In the Other World, it became annoying to find the matching color AND matching expansion(s)
When drawing a Mythos card, you're used to looking immediately at the gate location. To then look at the board and start figuring out what's happening, but to then notice the card is not in an expansion you're using, is kind of anti-climactic. There should be only one draw of Mythos cards each turn. It represents the big dramatic turn of events that round.

If I were you, I would go through items/skills on a draw-by-draw basis, but separate out the unused Other World, Ally, and Mythos cards before a game. How you handle Arkham encounters is up to you; with the draw method I use, it is crucial that cards never get removed.