Okay, so I'm probably not the first person to try this, but:
A small time ago I tired of mixing every mythos card together, and decided to just miss the base game mythos and one other expansion at a time, as per the reccomendation of members of this board. I found the quality and excitement of my games increased tremendously, and if you haven't tried this I heartily encourage it. The work required to shuffle decks together and then separate them once finished is really quite minimal.
Unfortunately, I grew addicted to the rush of the new, concentrated decks and started to require concentration in higher and higher doses. So I tried eliminating the base game's mythos entirely; playing only with the mythos cards provided by the expansions (and shuffling in The Story Continues just to make the rules work out okay). The results varied:
Kingsport: Without a doubt, this works the best. There are enough cards that the Mythos deck that I didn't have to worry about repeats, and they were all gate openings in Arkham, with a few bursts. Kingsport suddenly felt alive, as monsters appeared there, events happened, and rifts actually opened (thanks to headlines and rumors). It really brought the focus onto Kingsport, and this is now my preferred way to play with that board.
Black Goat of The Woods: This also works very well, though the mythos deck becomes awfully thin. Gate bursts and Arkham portals make for a nice, difficult game while keeping the theme in focus. Two double doomers are balanced out by strange sightings cards. Best played with Shub-Niggurath and The Black Goat of the Woods, for maximum theme.
The Curse of the Dark Pharoah: This deck alone suffers from a lack of seal bursts, but you'll actually use that dusty old exhibit item deck for once. The focus stays on Arkham, so I wouldn't use any expansion boards (they'll be awfully dull). The theme is good and concentrated, but you'll be nailed by that awful clothing drive environment quite often. Only time I like playing Tsathoggua. I find this game to be difficult, but not overly so.
Dunwhich Horror: This still works pretty well, and will provide for a very challenging game. It seems that gates open in Dunwhich about every other turn this way, so investigators will have to be permanently stationed there, enjoying the Shack's hospitality before rushing back into endless battle with a sea of monsters diving for those vortexes. Gate bursts are pretty common, so expect to slap down at least seven seals for a victory. When combined with the Dunwhich Horror herald an awakening becomes an almost certainty. These have been some of the hardest Dunwhich based games I've played.
Innsmouth Horror: There is a bit of a jump into 'not working well' here, I'm afraid. As Innsmouth contains only portals to Innsmouth, Arkham becomes a very boring place, used only to stock up on clues before desperately trying to stop the inevitable filling of the deep one's uprising track. Once all four portals open monsters will come spilling out constantly, rushing for the vortexes. Then, if you seal one (assuming it won't have a gate burst, which is devastatingly common) any gate opening there will add yet another token to the uprising track. Add this in to the fact that there are only four portals on the board, so you can't really win with seals, and you have a difficult, perhaps broken game on your hands.
The King in Yellow: This, i'm afraid, just plain doesn't work. Six of the twenty seven mythos cards are "The Next Act Begins" meaning it is very probably you'll run into four or five of them over the course of a game. So... y'know, 8-10 doom tokens, cut with removing elder signs or just straight up losing. The risk of losing by Third Act is extremely high, and throw in the double doom cards from the deck (two, I think) and you have a nightmarish, painful game. I've never won this way and I expect I never will.
So, your thoughts? Has anyone else been playing this way? What are your findings if you have? Am I just being a wimp about Innsmouth and King in Yellow?
! Also, it shows us the true Father Michael
!