To us, the biggest difference is that Connect _also_ supports the gRPC and gRPC-Web protocols. That lets your code interop with a much, much larger ecosystem of tools and systems, many of which are better-supported than their Twirp equivalents.
We designed the Connect protocol and the Go APIs to make multi-protocol support seamless. Server-side code supports the Twirp-like protocol and the gRPC protocols simultaneously by default. Clients can switch protocol with one option, no other code changes required.
It was the #3 issue opened on twirp repository, but they never settled on a solution.
https://github.com/twitchtv/twirp/issues/3
One super underrated feature Connect offers for Go devs is access to the request/response headers. No more plumbing incoming/outgoing context :phew: