orcs as neandertals
The first 3e game I ran was a prehistoric game, and I figured orcs were primitive humans and elves were advanced humans. It didn't really come up in game, but that was my thinking.
True, neandertals were probably no more aggressive than humans, but that's not saying a lot. And two groups with obvious physical differences often go to war against each other.
Most evidence shows that Neandertals and early modern humans didn't live in the same areas, but that was when there was a *lot* more open space and people lived in nomadic bands (which usually max out at about 30 people). In a medieval setting where people are competing for resources, conflict would almost certainly break out.
Really, it comes down to mood. If you want to play orcs as a seperate vein of humans, and give them a neandertal-type culture, sounds cool. Portraying them as the Tolkien-esque "servants of the Evil One" wouldn't mix too well with that.
Oh, and check out Michael Chrichton's Eaters of the Dead (or the movie, the 13th Warrior) for Vikings fighting Neandertals, or Robert E. Howard's Bran Mak Morn stories for Pictish Neandertals.