What's the "biggest change we've ever made" in Magic?
This was to do with Vision design (see podcast #495 and #496) and the introduction of the design play team. There's an article here where Maro talks about it from October of 2017.

It's a very interesting article and gives me high hopes for the future of Standard considering how much of an issue they've been having in terms of creating balanced and fun Constructed environments recently.