I still think the biggest things hurting this show are the lack of villains, and the lack of serialization. They may have waited a little too long to switch away from standalone procedural episodes.
Also, many of the episodes are weak in the opening 15 or 20 minutes, and only get good from about the middle on. I'm not sure why this is ,but I think it is a weakness in the early investigative scenes. The FitzSimmons technobabble tends to make me glaze over a little, and as a Star Trek fan, I have a stronger tolerance for technobabble than most people.
Another problem is the premise itself. The basic idea of a marvel comics show with no superpowered characters is a fairly timid premise when you think about it. I do expect this to change. Somebody (maybe Skye, with her mysterious parentage, or maybe Coulson with his mysterious resurrection) will probably get some kind of superhero advantage before long. If they weren't already planning this I expect them to implement it soon as a kind of panic move now that the ratings are tanking, and the show will be better for it.
AOS isn't realistic enough to function as a standard procedural, or as a spy show, and that's fine. It shouldn't be realistic or gritty or any of that nonsense. Instead they need to amp up the fantasy elements. Make it more Marvel, make it more comic book.
And I don't get the complaints about Skye at all. She's still my favorite character other than Coulson, and I liked her better than Coulson before the last couple of episodes. She's cute, she's funny, she has principles and won't let rules get in the way of what she believes. She's a Gryffindor in a sea of Ravenclaws and Slytherins. And she still does a better job delivering the whedonesque dialogue than anybody in the cast.