I read an article in an old Dragon quite a while ago on PCs who got sent back to a pre-history era, and ever since then I've always had one in my campaign worlds, though I've never used them as of yet.
To me, it'd be great fun to (as that article talked about) have some sort of temporal accident drop the PCs off there, as it becomes a great blend of fighting off the native monsters, but also surviving the environment.
For example, divine spellcasters have to deal with the fact that their gods don't exist/haven't come to this world yet. Essentially, since there aren't humans yet (there might be some proto-humanoids, but nothing even close to a true civilization for them), there are no gods among humans, or even relatively close deities for them to draw power from. The absolute closest that there might be would be demigods (who are physically present on the world) who are little better than animals themselves, representing aspects of nature, such as survival, death, hunting, etc. That old Dragon article on the demigods of the Primal Rage video game was a great idea in that regard.
Likewise, arcane spellcasters have it a little easier, but spells with material components can be harder to use, since gathering those components can be a lot more difficult now.
Repairing weapons and acquiring new missle weapons if existing arrows and such break is much more difficult. Gathering food can be harder since rangers and druids weren't trained in this environment, so Survival checks can take a penalty.
In terms of monsters, I prefer to focus more on "natural mutations" than things like evil Outsiders, since the latter are so timeless that they go against the grain of the alien, isolated feeling I'm trying to create. Rather, the PCs will meet things like proto-dragons, gigantic sea monsters, huge burrowing worms, walking carnivorous plants, etc. Basically, monsters that are natural products of a world where nature is still wildly experimenting with creating new lifeforms.
