As mentioned in the previous excellent answer, the themes of God and religion and materialism and corruption are major in Wise Blood; however, there are also themes of moral corruption, change and transformation, free will, flesh vs. spirit, conscience, appearances and reality, and the American dream.  Enotes explores all of these themes, in depth, at the link below.  Sometimes a reader may view one or more of these to be the major theme, surpassing what others may see as the single major theme.  It actually depends on what the work means to or how it speaks to the individual reader.  Take a look and then, using the information here as a guide, decide which theme you deem most important.  Brenda