There are a ton of things that are different between your situation and what I'm familiar with, and I'd want to see a ton more details to actually have a ssuggestion. However, as one random thing that we've seen make a difference: Adjusting the "max_idle_instances" seems to impact billing pretty strongly for our application. At this point, we run nearly all our modules with a low value for max_idle_instances (e.g. 1), since it seems to decrease cost a fair amount, and haven't observed a latency impact (we also haven't monitored it TOO closely and we aren't super latency sensitive). The way we see this as a problem: On the App Engine dashboard, if you select "instances", watch the "billed instances" VS the "active instances". In our case: we see "billed" to be usually below "active." When this was a problem, it was higher.
Good luck, and if you figure out what was happening, I'd love to know (a) what and more importantly: (b) how you tracked it down.
Evan