What should be the focus of my thesis statement about "Wise Blood"? Would a thesis focusing on irony be effective for "Wise Blood"?
Your thesis statement should focus on whatever point you are trying to make in your essay. If your intention is to discuss the irony in O'Connor's novel Wise Blood, then that's what you need to say in your thesis statement.
The thesis statement tells the reader what to expect in the rest of the essay. You might call it a condensation of the whole essay into one sentence. I've attached to this answer two articles that will be very helpful to one. The is the enotes definition and examples of thesis statements. The second gives suggestions on how to write a thesis statement. I'm sure you'll find some good advice!
Your thesis statement may very well concern irony, however it should also illuminate a significant aspect of the work you are discussing. Ideally, your thesis would explain both how irony is used within the story and what purpose/what effect this irony has. As you are writing your essay, you would explain upon how irony is used primarily by citing examples within the story of moments of irony and then to answer the second part, perform a close reading of the examples you have chosen and relate them to the work as a whole.
Be sure to also draw distinctions between the different types of irony or to clarify which kind of irony you are focusing on.