Well, the Humid Bone Forest is famous and the only reason why an Uchiha with MS (like Itachi), would start to shit himself after mentioning a similar place, is if a Sage Mode using person already totally owned some other Uchiha with MS. Make sense, I guess, thought it's still not fully confirmed.
The Senju, were called the clan of the forest before Hashirama appeared. It seems that they had a connection to the Humid Bone Forest, similar to how Juugo's clan had connection to Dragon Cave (was Juugo's clan name revealed ?). Being born with Mokutoun, might be the effect of his ancestors associating with the Hermit Law. Of course, it might be that Hashirama had a different parent than Tobirama and simply that parent took him along to train him, while in the meantime, their mother met another man and had a second son, or something like that. The Senju (as Senju) started battling with Uchiha only after Hashirama became their leader.
The fact that all 3 places are so famous, suggests that there were famous sage mode users steaming from them.
At the beginning of the series, Sasuke mentioned that people with special eyes, seemed to posses powers that could top: genjutsu, ninjutsu and taijutsu. He mentions that Sharingan is one of those. At first I though that he meant only inborn Doujutsu, but now that I think about it, each Sage Mode gives you special Doujutsu and each Sage Mode allows you to use Senjutsu, which is a more powerful form of the 3 above. This means that half of the Doujutsu are effects of the Sage Modes (we have 3 known Sage Modes and 3 known great Doujutsus).