Or at least any that supports gathering and utilizing profiling information. Last time I checked, that didn't include Rust yet for instance, but my information could be out of date there.

rustc does support PGO, but I don't know how mature the support is. https://doc.rust-lang.org/rustc/profile-guided-optimization....

Can I create profile data by running the instrumented binaries through testcases? Perhaps integration test cases which represent typical end to end functionality of my application.

Unit tests are a bad fit, you need to run a test that is representative for an actual work load.

A unit test that tests code that’s cold in practice would make it look like hot code, and be counter productive.

Yes you have to do that. That's how PGO works.

Rust does support PGO