Simpler. But "simpler" requires or implies a comparison. Simpler than what? And prayer can be a count noun, so maybe you mean "Most prayers are simple." If there is no comparison, we use simple.

1. Most prayer are more simple. 2. Most prayer are simpler. As Alan says "simpler" is a comparison word, so you need at least 2 things. So "prayer" should be the plural "prayers" in both sentence. Assuming you change "prayer" to "prayers" in both sentence, then 1 is not correct by itself. You might say "Most prayers are more simple than that". However, I don't think that an average English speaker would use "more simple", it sounds clumsy. 2 "Most prayers are simpler" would be a complete sentence, but in context, it would be "This prayer is too long. Most prayers are simpler" -- this gives you the comparison that Alan talks about..

You can actually check this is a dictionary. If one dictionary doesn't give you the answer you want, use another. http://www.thefreedictionary.com/simple says.... sim·ple adj. sim·pler, sim·plest