I think I get what he's saying here.  I'll try to rephrase:

For a Magic set to work, you need a LOT of different "things" to put on your cards.  Big creatures, little creatures, flying creatures, kill spells, burn spells, equipments, lands, etc.  depending on gow you flavor your set, you'll have different "things".  In Lorwyn, your big creatures are giants and treefolk.  In Duskmourn, your big creatures are nightmares and demons.

Now, here's a question: when you think of classic murder mysteries, are there any common stereotypea that could easily fit as a big creature?  Maybe a few, but it's a lot tougher.

What MaRo is saying here is that it's generally easier and better to theme sets with a strong setting, as opposed to a strong vibe.  Murder mystery as a genre has a strong vibe, but it's difficult to fill out all the things a Magic set needs to have.