Among anime and manga fans, the cost of obtaining a Philosopher's Stone in the popular series Fullmetal Alchemist is well-known for being particularly horrific - in Tite Kubo's Bleach, however, there's an object which demands an even greater sacrifice.
In Bleach, near the end of the series, it's discovered that the Soul King, who presides over the realms of living and dead alike, and monitors the balance of souls in each, is hidden away in another dimension. In order to reach this destination, a person must possess an object known as the Oken, the key to the Soul King's palace. In a rather grotesque twist, it turns out that the Soul King's Royal Guards have these Oken literally fused to their bones, making it so that the only way to reach the Soul King is by being a member of his guard or being accompanied by one. Additionally, the only person outside the palace who knows this is the Head Captain of the first squad of the soul reapers, and the information is never written down. While it theoretically makes the palace completely immune to invasion, this safety has a high cost.
The process of creating these Oken is complex, but the first step is to locate some consecrated land of an appropriate size. Conveniently, Ichigo and company's home of Karakura Town happens to fit the bill. The second ingredient in the ceremony is 100,000 mortal souls. The result of this ceremony is not only the Oken, but a new living Royal Guardsman with that Oken imbued into their bones.
In Fullmetal Alchemist, a great many people in the ancient nation of Xerxes were sacrificed for a Philosopher's Stone, but their souls continued to exist inside the stone until it was destroyed. Additionally, the minimum number of people needed to create a Stone is actually much smaller than that, since it's known that the Amestrian government was producing them out of death row inmates, using as little as a few dozen. While there did seem to be a connection between power and the number of sacrifices, there's no indication of how many people were in Xerxes at the time, which was undoubtedly the largest incident. The Philosopher's Stones also function as the hearts of homunculi, ageless beings with powers far greater than a human.
Incidentally, this also describes the Royal Guard. The Oken provides them with unaging bodies, and they can seemingly be revived endlessly, as part of their service. Five Royal Guards are shown in the series, indicating that this procedure has taken place at least that many times, and cost at least half a million human souls. The villains in the Thousand Year Blood War arc stand against the Soul King to change the world of Bleach, and with this kind of behavior, they might just have a point.