The Sign of Four is a fascinating addition to the Holmes stories, giving us fresh insights into each of the characters and their stories. Here are some key events that add layers to the series as a whole.
One key event is in the very first scene, where we find Watson observing Holmes indulging in his cocaine habit. As a doctor and a friend, Watson is concerned and disgusted by Holmes's habit, and he is distressed at Holmes's apathetic response to his attempts to cure him of it. Holmes, on the other hand, is unmoved, and he denies being actually addicted to cocaine, attributing his usage to the absence of a mentally stimulating case. This sets us up to understand both the doctor's continuing concern for his friend's health and Holmes's unusual views of his own drug usage.
Another key event is the introduction of Miss Mary Morstan, Holmes's client who eventually becomes Watson's bride. Throughout the books, Watson repeatedly falls mildly in love, but it is the gentle and pretty Mary Morstan who finally claims his heart and his hand. Her appearance in the chronicles adds another layer to Watson's story and gives us a bit of insight into his character as well as hers. We find neither Watson nor Mary are mercenary people, as they are both more relieved than anything to find that the chest, which was supposed to make Mary "the richest heiress in England," is in fact empty.
Other key events that give us some insight into Holmes's character occur when we see his deductive reasoning in action. In the beginning, we see him idly deducing precisely where Watson has been that morning and describing the origins of his watch out of sheer boredom. Later in the book, we see him put those same skills into action on more important matters, such as the examination of footprints (during which he deduces that one set was made by a man with a wooden leg, and the other by a very agile, barefoot man, whose footprints are stained with creosote) and his discovery of the poisoned dart in Sholto's scalp.
In this book we also see Holmes using his clever disguises (he disguises himself as a sailor to search for the Aurora), and we are given a glimpse into how his Baker Street Irregulars operate.