The street-level CHAMPIONS campaign I ran for about 3 years during the 90s featured some religion-themed characters, one a PC and the other two NPCs. It started with an NPC hero who was there to act as a potential rival, ally or balancing factor for the PCs, and to be sort of the opposite of the grim, dark characters who were so prevalent back then. Redeemer was a fundamentalist Christian who was essentially a very skilled athlete (gymnast, boxer and wrestler) who also had several dice of luck that only worked if he was certain of the righteousness of his cause, and which he considered "divine providence." He was openly Christian, even incorporating the cross into his costume, and was extremely law-abiding.
The presence of this character prompted one of the players to make his character, The Reverend. Essentially a religious version of Stick (Daredevil's mentor, from the Marvel comic), with a couple of low-level psychic powers and a mind link to his follower (a seeing-eye/attack dog), The Reverend was a blind street preacher who took a bit more active role than most in fighting street-level crime. He was also less dogmatic than Redeemer, leading to some memorable PC/NPC interaction along the lines of theological and philosophical debates, particularly since the Reverend wasn't beyond breaking the law to serve the greater good.
The third religion-themed character in the campaign was an NPC villain, Brother Night. He had a public persona as a minister and evangelist, the Reverend Thomas Knight, who spoke out against lawless vigilantes and other negative influences on society, but was also secretly the cult leader/vice kingpin Brother Night. In addition to being one of the Reverend's Hunteds, Reverend Knight/Brother Night served as a stand-in to corrupt, real-world religious figures who pose as moral watchdogs and stick their noses into others' business but aren't particularly moral themselves.
Anyhow, the religious themes didn't cause any problems as handled in that campaign. The players were all mature, and having someone represent religious POVs served to deepen the campaign, in everyone's opinion.