This show is quite hard to describe. It centres on the character of Grace Hanadarko, a boozy adulterous out-of-control detective, working for the Oklahoma police force. It is also about Grace's relationship (or lack of) with God, and a lovable aging angel called Earl. But this isn't just for Christians, and it is made clear that Earl is non-denominational, with 'clients' all over the world. It's also a pretty raunchy show, with a fair amount of moderate violence, so I doubt it would appeal much to devout American Christians.
Grace's best friend (another brilliant actress) and brother are both Catholic (her brother is a priest), and so would quite like her to go Mass with them, but Grace has other ideas. In fact, she is extremely resistant to anything to do with God, at one point literally wrestling with Earl on the ground. She has a deep-rooted distain for religion, which we learn is completely understandable, and at no point is she meant to be judged by the audience. Seriously, you don't have to be religious to like this show (I'm not), but it probably helps to have a little curiosity about the whole thing. There is also a cop show element to each episode, with a new case for Grace to help solve. But this is really secondary to the drama of Grace's private life. I can't imagine anyone else in this role - Holly Hunter is perfect.
This show is really something different, and the acting is great - not just from Holly Hunter, but also the other detectives, her lover, her best friends, her brother, and of course Earl. Every episode is great.