The interview is by Brian Michael Bendis, himself no mean writer, and it is very interesting for anyone interested in the challenges of writing groups of characters, movies, etc. But he made an interesting point about the differences between genre fiction and what I think of as "mainstream" fiction:
WHEDON: First of all, there’s no genre I’m not interested in. The sensitive family drama, I have trouble with. Apart from that, there’s nothing. Everything’s good. Musicals, comedies....
BENDIS: What’s the trouble with sensitive family drama?
WHEDON: I don’t know what the structure should be. I never studied writing. So genre lends me certain crutches or signposts. Here, they’ve gotta sing, they’ve gotta be scared, they gotta have action. I just saw a great production of “All My Sons” and I was like, “Oh yeah. That’s the way you’d do [drama].” The way the stories and revelations come out about the family. Besides the fact that I don’t know structure, I like to be one step removed. I like the fantasy or the singing or something that takes you a little bit away from where you’re at. Because I don’t want to write about me. I mean, I’m in there obviously, but I want to make that more general. I want that to be more universal as opposed to, “I’m 40. I’m writing. I’m boring and depressed.” I mean, it’s like, “Great. That’s a fascinating story... buddy.”
I mention this in my book, but structure often reflects the motives -- specifically the thoughts underlying the motives: goal, action, blocks, help, reaction. The differences, like those of the motives, are in nature of the goal and the actions rather than the structure as such.
It doesn't surprise me that Whedon prefers genre fiction, because there is an understood structure or at least certain assumptions. In mysteries/crime fiction, a desire for justice is often assumed, or even that "murder will out." Dorothy Sayers referred to it as "our most moral literature." That means you have someone discovering what really happened. That has clear implications for creating conflict, such as someone preventing you from finding out the truth, for example.
Fantasy, of course, has the monomyth: young person discovers s/he has a secret destiny, overcomes many obstacles while guided by wise and usually elderly mentor to achieve destiny, achieves destiny, sometimes dies and may be resurrected. Everything from The Hobbit to Star Wars has this structure.
And Romance has the "boy-meets-girl, boy-loses-girl, girl-gets-eaten-by-horrible-monster" -- oh, wait, that's Horror. Anyway, you know the Romance plot. Whether it is tragedy or not depends on whether it is a wedding or a funeral at the end.
The fun thing about these structures is, because they are so deeply planted in our subconscious minds, we can throw people for a loop by breaking those assumptions selectively. Could you have a romance with a funeral at the end? Perhaps in a vampire romance. Joss Whedon happens to be gifted at playing on precisely those assumptions, which is why I enjoy him. He can take a hackneyed idea and plot, play it for all it's worth, and then ring changes on it that are hilarious. Do it too much, and you feel manipulated, so you have to be careful...!