The biggest problem has been Google Play Services, but now, with Granular Dependency Support, you get only the packages you need. That means instead of nearly 30k methods, take it or leave it, you'll use up only a few thousand method table entries.
In general, don't go nuts with big monolithic libraries. There's a lot of over-engineered Android code out there, especially when you have big, well-funded development teams.
If your app still break the 64k limit, maybe you are stuffing too much into one app. Android makes it fairly easy for multiple apps to share data and other components.
