My current board game is based on the Lewis and Clark expedition in 1804-1805. One of the things that really appealed to me about the theme and setting is that there were a ton of hardships the expedition had to face, including horrible weather, disease, hostile Native Americans, and just flat-out getting lost.
I wanted to really leverage the Native Americans in particular as I thought their contributions to the story were pretty significant and interesting. At some times, the Natives greatly assisted the explorers. In fact, without them the explorers may have failed or perished.
However, in other cases, the Natives were hostile or supposedly stole from the expedition. This is great variety and frankly, I don't necessarily blame the natives for being hostile. After all, the Americans and Europeans didn't exactly greet them in friendship.
It's a tricky balance and it can be a very touchy subject. It's very tempting to use words like "savages" and acts like "scalping," but I don't think that improves the game, it doesn't match the theme or history, and it'll probably offend someone.
I've tried to stick to the history I've found on Wikipedia and other sites and go from there. My cards won't always be 100% factual, but they'll be within the ballpark. For example, in one event you can negotiate with Sacajawea's husband to bring her on as a translator. In another case the Blackfeet steals things from you. You attempt to trade with the Otas and the Omahas may give you fair warning of an impending attack.
There is history to mostly back this up and as a result I think I've created something that's entertaining, fairly presents the various entities involved in the history, and most importantly, leads to a fun game.
Plus, I've bolstered the mostly factual with the completely absurd with entities like the Missouri River Piranha and other less factual creations.