I believe our single biggest mistake from a technical side was not reigning in our use Django ORM earlier in our applications life. We had Twisted services running huge Django ORM operations inside of the Twisted thread pool. It was very easy to get going, but as our services grew, not only was this not very performant, and it was extremely hard to debug
Django has in many ways become the industry standard in regards to fast development - but it, as so many other ORMs, does not scale and produces horrible SQL-statements. Also for many applications I find Django to be a huge overkill - and in more recent times I've focused a lot more energy using microframeworks such as Flask and Bottle.