Story:
Defiance continues from where Legacy of Kain: Soul Reaver 2 ended. In Soul Reaver 2, Kain saved Raziel's life by drawing the Soul Reaver from him - Raziel was meant to enter the blade and become its soul-devouring spectral half. This causes a time paradox that changes Nosgoth's history for the worse, and separates Kain and Raziel.
Kain's part of the game follows him seeking Moebius the Timestreamer, a time traveling mystic for answers to where Raziel is, how he has changed time, and later following a lead Moebius gives him to explore a Vampire citadel. ...
Raziel's part of the game begins five hundred years later during the time of Blood Omen. Held captive by the Elder God, Raziel escapes his master and travels about Nosgoth hoping to find a way to avoid his fate of being imprisoned in the Soul Reaver. ...
Source: Wikipedia, "Legacy of Kain: Defiance," available under the CC-BY-SA License.