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It all boils down to simply knowing what your players are comfortable with, and what they're not comfortable with, and working with them. There really isn't anything more to it. Everyone is at the table to have fun; the players are volunteering their time and agreeing to play in the GM's campaign, and the GM should in turn ensure that the players have a rich, enjoyable experience.
If it's a matter of the players being uncomfortable portraying characters in a setting with a multitude of gods due to their real-world religious inclinations, I can tell you from personal experience that Pathfinder does NOT require a polytheistic setting; a monotheistic world with a singular, good deity can work just fine. As Javaed mentioned in his post, I home-brewed a campaign setting with a fantasy analog to Catholicism, where the opponents the PCs face are demons and undead. The player characters are true heroes who battle supernatural evil and protect people, so I conclude that portraying a "murderhobo" isn't required to have fun in a campaign, either.