Few problems I want to address in this thread.
One, it is kinda obvious that Madara did not die at the Valley of the End; we can guess, with more information about Hashirama's persona, that Hashirama didn't have the heart to kill his best friend.
Two, the MS is activated from the feeling of losing someone close to you, when you are actually there to see it. It doesn't have to be your best friend, just someone you care deeply for. So it really isn't that interesting, to me, when we know that during that time people were dying left to right.
Third, Mito and Kurama. We can easily speculate that Kurama was sealed into Mito AFTER the Valley of the End incident. Most likely when Hashirama beat Madara he ultimately ceased control of Kurama and put into his wife because she was special out of the Uzumaki clan.
Fourth, Madara couldn't have activated the Rinnegan at the Valley of the End. The only reason he was able to activate it in the first place was because he was able to obtain Hashirama's DNA, from the Valley of the End, and implant it into his wounds; with the Rinnegan emerging when he was old and about to die. But, since he had awakened the Rinnegan, and had some of Hashirama's DNA, he was able to use the conjuction of the two to then extend his life even further up until the point he was able to pass down his plans to Obito, which was just a coincidence.
Fifth, this now leads me to believe that the Rinnegan is able to be activated when the blood of a Senju and Uchiha come together (I'm guessing AIDS didn't exist back then), since the Sage of the Six paths son's where the ancestor of the Senju and Uchiha.
Sorry for the long ass response just wanted to clear some things up.