The relevant part of the story is pretty simple. Brothers Dean and Sam are searching for Metatron, an angel who fled heaven. They have part of a "demon tablet" that may provide a clue.
Here's what the Supernatural wiki has to say about it, with my comments:
8.21 The Great Escapist
More important, the singular "God" is a Christian concept, not a Native one. I don't think any Native religion was monotheistic, and no one called their chief deity "God."
Colorado has only two Indian reservations in the southwest corner, but a fictional tribe is tolerable for storytelling purposes.
The Two Rivers reservation and hotel appear to be in the mountains, which would put them close to the towns of Loveland, Fort Collins, and Greeley and not that far from Denver. In other words, the deserted hotel doesn't make sense.
If Route 34 doesn't get much traffic for some reason, the small casino/hotel would go out of business. More likely, it would draw visitors from the nearby towns and from Rocky Mountain National Park. It would do decent business and the tribe would build a larger casino.
This is a variation on fictional reservations located in the desert or the wilderness far from "civilization." This reservation is close to "civilization," but Supernatural portrays it as forlorn and abandoned. I presume the reason is because a bustling reservation business with lots of visitors wouldn't convey the same mood.
Supporting the point, his character is listed as "Hotel Manager." In other words, he's a function, not a character with a name or a life. He exists solely to advance the plot.
Yeah, that's a big problem. A tribe whose religion is based on a visit from a Judaic angel? Is Two Rivers supposed to be a Lost Tribe of Israel?
Here's the story on the original Metatron:
This supernatural bit might not be bad in another story. But there are only two Indians in this story, and one or both are "supernatural." They serve or believe in their master, a white Judeo-Christian angel. They have no independent culture or existence beyond their devotion to Metatron.
The The Great Escapist is a good example of how Hollywood takes one or two steps forward, then one or two steps back. Steps forward: featuring modern Indians at all, and using a Native actor to play the main one. Steps back: the mistakes and stereotypes, especially the implication that Native religion is derived from Judeo-Christian beliefs.
It wouldn't have been hard to do this episode well. Make the clue something other than a petroglyph referring to God. Show several Indians in and around the hotel and make it look prosperous. Have Metatron hidden in a remote part of the rez, not upstairs.
Or just have Metatron hidden in an isolated non-Native rather than Native community. Joseph Smith received tablets, after all, so tie Metatron and his tablets to the Mormons somehow. Indians don't have to be responsible for every supernatural situation in America.
For more on Indians and the supernatural, see Metatron in Supernatural and Bad Kids Go to Hell.