I've watched Red vs Blue for about 10 years now, and have always enjoyed the humor and writing. I have played Halo and watched friends play it during the LAN party days (pre-XBOX live), so I know a bit about the video game series, but you don't need to know the mythos to enjoy the show.
There is profanity used, in copious amounts, so sensitive ears would be best to stay away. The writing is smooth, the characters are well developed, the storyline becomes increasingly complex. All around well thought-out and intricate.