So, why'd I choose Inseparable for the listing name? Just about any fan of this relationship will tell you that Prue and Piper were closer to one another than Prue/Phoebe, Paige/Phoebe, Piper/Phoebe, and Piper/Phoebe.
While we saw Prue and Phoebe disagreeing with one another on a regular basis, and at times fighting with one another, we rarely ever saw Piper and Prue disagreeing with one another. And I don't remember them ever fighting amongst one another. Prue may have had trouble telling Piper that she loved her in the beginning of the series, what she failed to say in words, she had no trouble showing in her actions. Prue and Piper both could have moved out of the Halliwell Manor long before they became witches, but both opted to continue living there. Whether it was out of some feeling of obligation to their Grandmother or because they just didn't want to move away from one another they stayed together under one roof.
The thought of living away from each other was terrifying to them, but the thought of  the other one dying was unbearable to them. The first example of this being the second season episode, Awakened. When Piper contracted a deadly virus. Prue had talked Phoebe into going against the rules in order to save Piper. Prue didn't care about the consequences of using their magic for personal gain, all she cared about was saving her sister...not the Charmed Ones or innocents...but her sister.
The second example of this was the third season finale, All Hell Breaks Loose. After the sister's were exposed on television to all San Francisco, Piper was shot and she died shortly after that. There is just no way I can do that scene justice by describing it in words. The raw emotion of Prue...and Shannen's performance...left most viewers naming this the best moment of the third season. There really wasn't any words spoken by Prue in the scenes. Which made it that much more powerful. The fans knew Prue had seen her mother dying, and now to watch the sister she was closest too...her best friend...lying on the hospital bed dying?  It was too much for Prue. But as the fans know, time was turned back and when it did, Piper was spared. But when time was turned back, it was Prue who lost her life.
Which brings me to the last example. The fourth season premiere, Charmed Again. Piper showed the same raw emotions over Prue's death that Prue did over Piper's 'death' in All Hell Breaks Loose. What Shannen wasn't able to convey in words in All Hell Breaks Loose, Holly was certainly given the chance to shine with it. Piper had an extremely hard time coming to terms with losing her oldest sister...and her best friend. This is another episode where I can not do it justice by describing it. Just as Shannen was the standout actress in All Hell Breaks Loose, Holly was easily the standout actress in Charmed Again 1&2. I really believe most of Piper's anger came from the hurt over not being able to say goodbye to her sister. She lost her mother without being able to say goodbye to her, and now she loses her sister...her best friend...without getting the chance to say goodbye to her as well.
I think the thing that made Piper and Prue's relationship so believable to the viewer's is the fact that Shannen Doherty and Holly Marie Combs are so close to one another in real life. In fact Holly was quoted as saying the reason she initially didn't like Rose McGowan on the show at first was because Rose was brought onto the show so soon after Shannen was fired. And the biggest reason why Piper was so angry at Paige was because Holly said that she was displaying her anger over Shannen being fired.

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