In my experience, the default VM size is so slow, you probably don't want Nix on a workflow that doesn't already take minutes.
Even with a binary cache (we used R2), installing Lix, Devbox and some common tools costs us 2 1/2 minutes. Just evaluating the derivation takes ~20-30 seconds.
You can cache arbitrary directories in github actions, but the nix package cache is enormous and probably bigger than GH's cache system will allow. Restoring multi-gig caches is also not instant, though it still beats doing everything from scratch. Might be more feasible to bake the cache into a container image instead. I think any nix enthusiast is still likely to go for self-hosted runners though.
The default cache action also has issued with anything that isn't owned by the runner user, and caches are per-repository, so you can't just have one cache like you do for binary caches.
Even with a binary cache (we used R2), installing Lix, Devbox and some common tools costs us 2 1/2 minutes. Just evaluating the derivation takes ~20-30 seconds.