CPython is very slow at various things that are common, like function calls and attribute lookup. There is no good reason for this and few runtimes are quite this slow. This sort of overhead adds up and is often annoying to deal with.

Yes, I have run non-trivial applications on PyPy and they were significantly faster. Its only downside is libraries that depend on CPython extensions, but there are few of those left.

Pandas doesn't do much for removing function call overhead. I don't necessarily have large mathematical datasets, I just want my web service to be easier to write, by not having to care about what CPython is terribly slow at.