I just finished *removing* jQuery from Mycena Cave, and I'll probably never use it again because of the following combination of issues:
It's a lot of code - it's comparatively slow, and a largeish download
There's no good way to structure your code. Enjoy putting everything into a single $(document).ready(function() {});
Utter hell to extricate from your codebase
Concerns re: security and keeping it up to date
To elaborate on the last -- version bumps periodically security fixes, but also breaking changes. Because I have better things to do than follow the upgrade guide every time they release a new version, it falls out of date, and then becomes harder and harder to update (because you end up with a larger and larger list of breaking changes for which you have to scour your poorly structured codebase). And then you turn around and realize that you're running a version of jQuery from three years ago, there are many well-documented security vulnerabilities, and you can't upgrade it because if you do everything breaks.
My recent preference is Google Closure -- documentation isn't great and it's not really newbie friendly, but I'm loving the tooling and the compiler, and the way it's super easy to define good structure on your code. I recently re-wrote all of MC's frontend code in it, the compiler caught a number of long-standing minor issues, and the end-result is noticeably smaller and snappier to run than the old jQuery version.