The greatest challenge for organized religion in 21st century Western society is the deprecation of the priest class. The West has no want for any group of professional religious, at least one it would ascribe any prestige to. Appropriately, Western religious traditions are impacted by this. Catholics and Protestants have both seen a decline in their professional religious class.
That the secular West has little desire to produce such a class and Western religious traditions have seen difficulty repopulating this class attests to the dependency of religion upon culture. If not dependency, at least the difficulty religion has in separating itself from culture.
The situation in which religion finds itself is one, so far as we know, for which it has yet to produce an adequate model. Religion finds itself in a world of, to a greater extent, mass literacy and an overarching presupposition of self determinism. Previous encounters with such trends were often limited to the elite class of a given society. By the late 20th century, these trends had become more or less the norm, at least in cultural sphere of Western religion.
Barring a total societal collapse, if the arc of capitalism finally collapses under its own weight as Morris Berman has theorized, religion will have to live and breathe in a world in which it is considered little more than a personal choice and in which it is held to measure of intellectual standards, in so far as it has to contend with the majority of people it will encounter being literate and possessing the faculties to engage materials once reserved for the professional religious class.
Attempts at making religion relevant have by now proven themselves rather futile. If a religion presents itself as little more than codified pop psychology (see Cooke's Sacraments and Sacramentality for example) or an NGO with pomp and circumstance, said religion will quickly find itself grasping frantically to hold on to the ever changing demarcations of the cultural barometer. More importantly, it will fail to distinguish itself from culturally conditioned entities and trends by failing to address the components of the human experience that can only find a worthwhile narrative in the language of the supernatural or the transcendent.
Ultimately, the non-tangibles of human existence are the reasons why most people investigate religion or spirituality. Trying to keep abreast with social, economic, and political swings gets a certain "activist" segment to nod in approval. One often finds, upon examination, that such a segment places such and such activism at the heart of the their existence, religion lies somewhere on the fringe and is only seen in the colors of the aforementioned activism. Trying to keep religion relevant, moving away from the language of the transcendent to the language of NGOs, only serves to make the entire proposition irrelevant; a religion that does as much finds itself unable to speak to the concerns that more often than not lead contemporary Western audiences to examine a given religion or spirituality.
This is not to say that religion doesn't have any practical consequences. Indeed, religion requires a praxis of life. It is to say, however, if practical consequences are not spoken in the true language of religion, religion benefits no one by addressing them.