First: please stop referencing Seth Macfarlane when talking about American Dad!; Macfarlane hasn't had any creative direction in this series since season 1 and only provides voices for two and the main characters. The true creative forces have been Mike Barker, and Matt Weitzman.
Okay, American Dad! Blood Crieth Unto Heaven; this is probably the best creative departure from the norm the series has done. Not as fun as the hot-tub episode, better thought out than the hurricane episode. This is subtle humor at its best.
If you haven't, at the very least, seen a staged performance, or read a play, then you probably wont understand the amazing amount of love that went into animating every little nuance of a stage performance. There is "mistakes", live action introductions, act breaks, curtain calls, multi-layered stages, confetti, all of which are usually unnecessary in a televised production, let alone an animated one.
This episode is brilliant for honoring an under appreciated genre now days, and it needs to be noted for that. This isn't Roger shoving things up his ass American Dad!, this is thought provoking, genre pushing American Dad!. It's really nice to see a long running series trying new things, failing sometimes (not here), and trying to not stagnate... Like Family Guy (I said it, sue me.)