I saw it as this:
1. The boy faces different types of evil spanning history. But, keep in mind that, per the ending, the entire thing is a giant circle. I saw it as a statement that history literally repeats itself, and regardless of the tools we make to help us, our objectives/goals never really change; in other words, technology is no help to us and can in fact be used against us.
When you start, there is no man; there are only creatures (the beginning of time). There are artifacts left by man (crates, mine cart, boat), which in my opinion highlights the circular ending (we end up back where we started). I consider those to be remnants of the humans that existed before history repeated again.
After you deal with simple creatures, you finally encounter humans (the birth of humanity). They're very primitive humans, as you can tell by their blow darts and such, but they try to tweak what has been left behind to their advantages. Note that they don't actually make the bear traps. They just tie them on ropes and swing them at you. Same thing with the giant spider leg; they just hoist a rope to it and try to use it as best they can, with no technology of their own.
Finally, we end up in a modern-ish time (where we see the lit "HOTEL" sign as well as automated turrets), and even go to the future, where gravity manipulation is apparently possible. Note that the humans have been replaced by technology in these times (we no longer see people past a certain point); I feel that this a statement of not only the "evils" of technology, but also that we've lost our humanity with technological advances (machines replacing humans).
But, note that regardless of the obstacles you're presented with, human or not, the object is always the same: somehow advance to the next area (and find the girl, which I cover below). But, this objective gets harder as the technology advances (and, with it, the puzzles get harder and more complex) until the very last puzzle, where you have absolutely no control over gravity and the world is absolute chaos. Then, after you go through the glass pane (which I assumed to be a mirror), you end up at the realization that technology was frivolous all along, and that true serenity is accompanied by a lack of it. This is very notable considering the contrast in stress you feel between the last puzzle, and the slow, silent ending.
2. I think the girl just represents an arbitrary objective; she is an embodiment of the goal that society always works towards, the true "happiness" that is always sought, but never found. As far as the game goes, "finding your sister" represents the end of one's journey through life. The boy, who is a faceless shadow, represents the generic person throughout time, who is always trying to find this happiness. Yet, with the increasing complexity of technology, he is less able to do so.
He sees this happiness at one point (when he sees his sister but is forced away), but is unable to actually reach it. In the end, the only way he can truly find happiness is to symbolically break out of the technology that consumes him and embark down a simpler path. And, even then, we don't know for sure if he ever reaches it; the ambiguity in this case is actually a definite conclusion.
Well, that was a bit longer than I intended. Oops.