Mistkatonic Horror is a different kind of Arkham Horror expansion. It is an expansion for the expansions, so to speak.
Does that mean that if you just own Arkham Horror this set is useless? No, there are some parts that can be used to expand just the base game, however if you don't own any of the expansions you will likely be very disappointed by the price of the set for very little value.
One of the things that I find infinitely helpful are the cards included that detail "if you have this many people playing, monster limit is X, gate limit is X" and so on. They should have included these in the original set and have corrected that oversight with this expansion. It isn't worth buying for these alone, however.
What it is worth buying for is if you want to add cards or a hand full of variants to your game IF you own other AH expansions. ALL of the expansions (minus the original Curse of the Dark Pharaoh set) have new cards added with this set. While none of the cards add anything jaw dropping amazing, they do definitely add to the difficulty and fun of the expansions and the main game itself.
If you go in to buy this set as a normal AH expansion set, be prepared to be disappointed. If you approach it as an expansion of the expansions you already own, then you will likely be happy. There is roughly an expansion set, one of the larger expansion sets, worth of new cards. There are no new game boards, however, which makes the $50 MSRP seem a touch high to me.
I really like what it adds to the sets I own, but since there isn't a new game board I don't think the MSRP is completely justified.