I read slush earlier in the week. Biggest problem: not getting what the story is about. Speculative fiction is slippery and the worlds are new and different. Many writers failed to ground this editor with scene setting and primary conflict.
This is unusual. Typical problems include unoriginal concept, enough small mechanics issues that they add up to a lot of work for a tired editor, or perfectly good stories that just don't suit our magazine. (The whole "don't suit our needs at this time" is truer more often than you'd imagine.)
If you've got a particularly original plot or are blending genres or really stretching things in any particular direction, then you've got to be even more particular about setting the scene and establishing the story problem. Get the primary problem as close to the first page as you can, definitely in the first scene. Establish answers to the journalistic questions that every reader wants answered: Who? What? Where? When? and especially Why?
We love originality here at Electric Spec, but it's not a license to blow off the rest of your job as a writer.