Runes provide upgrades to your character, such as increasing your maximum HP by 5% or the number of Blood Vials that you can carry at a time. You will likely find several of these throughout your playthrough, so this trophy is practically unmissable.
The first rune that most players will be able to access is gained by following the path to the right from the Cathedral Ward lamp, going up the lift, killing the man in the wheelchair with the minigun, and then opening the chest in that room that contains a rune. See the following video guide for its exact location: