Hanging a piece of artwork over a mantelpiece is a great way to add attention to the room. In order to do this in a way that works, be sure to use a piece that is proportional to the wall and the mantelpiece. A good rule of thumb is to cover two thirds of the available wall space with artwork and try to avoid hanging a piece that is wider than the focal point over which it will hang.
If you cannot find a single large piece that works well, you may also use a collection of multiple pieces. Any piece being hung over something, be it furniture or anything else, should be at least 8 inches but no more than 12 inches above that furniture or other focal point; if one is hanging multiple frames together they should be placed 3 - 6 inches apart so that they do not crowd each other.