It took me three applications to get accepted at SS. Some of the ones that got thropugh on my first attempt were rejected on the second, so it's clearly not an exact science.
I think that RacePhoto's comments above are very good advice, particularly the one about downsizing.
The whole basis of the three D approach is Keep It Simple. This is an application, not the real photos. So don't get fancy with depth of field, or artistic interpretations. Shoot bright, simple, colorful, sharp images. Is there a D in shoot everything at 100 ISO? Some people think big and fast is impressive. Go slow, go small. We could get all involved in lighting and cropping and everything else, but the point is - First Get Accepted! :D
Yes, images that get accepted by one reviewer will get rejected by another. Things that the second tier agencies will take all month long, will get dumped by the top two. Except for some very standard / stock shots, there's a subjective factor to consider. Maybe the reviewer needs their 4 cents and is in a rush to reject things faster? Maybe it's late at night and they are tired and cranky? The phone just rang, they reached for it, hit the coffee and it splashed on the dog, which knocked over the side table and the lamp, as it ran out of the room... so they just clicked rejected on everything and shut down! :)
Don't expect to understand or get a real answer why something that's perfectly good, gets rejected for some vague obscure reason. Or for that matter, why something of mine, I'd personally say is marginal, gets accepted and sells? They run the show, just take a deep breath and keep on trudging up the hill.
I don't remember now, but I started at the second four to six sites, so I could get an idea of what was acceptable and what was a flop. I got fantastic advise and coaching from a reviewer on Lucky Oliver. Once I had a clue, I tried IS and SS. It was far from the almost anything goes of the easier sites. I think it took three tries (I forget?) for SS and I was sending in sold images from the other sites. IS was probably two tries. I had a 10D back then with a 28-135 middle range lens. Still one of my favorites, great for walking around and travel, but it's not a fantastic lens.
Getting accepted is the important first step, downsizing is playing the game to get through the door. It has nothing to do with what happens after you are accepted. Reduce the flaws, reduce the size, reduce the ability for reviewers to see any flaws. Turn out some assorted stock, stock, pablum and get in.
I deleted most of my early uploads from IS, but I'm pretty sure these were in the first batch accepted. Get the idea? Uninspired, one of 10 thousand similar shots, but it got me in the door?
(http://www.istockphoto.com/file_thumbview_approve/5772178/2/istockphoto_5772178-flag-high-on-a-pole.jpg)(http://www.istockphoto.com/file_thumbview_approve/5773195/2/istockphoto_5773195-white-casino-dice-on-red-background.jpg)(http://www.istockphoto.com/file_thumbview_approve/5773187/2/istockphoto_5773187-textured-surface-background.jpg)