You run your own authoritative DNS servers?

For us, Route53 is painful. We host a few thousand zones, and due to rate limiting on APIs, doing something like "Show a list of domain names" or "Give all the domains matching some pattern" were particularly painful. Upwards of 30 seconds to do a simple list of domains meant we were forced to cache locally. A local cache, combined with the fact that zone names are not unique in their system (possible to create multiple abc.com entries, which differ only in an internal id and the list of NS entries) made it hard to ensure that our internal systems matched "reality". Then the administrative nightmare of 3-4 different NS entries for each zone means customized, rather than generic, instructions for validating NS settings at the individual registrars.

All in all, it was not a fun experience with such a large volume of zones, but we knew we were an edge case.