You should never, ever, ever return a 2xx status code with an error payload. The 2xx series means "Success" and you're abusing HTTP to use it to mean anything else.
With regard to application layer vs transport layer, the 404 Not Found, 406 Not Acceptable, 409 Conflict, and many others errors are specifically application layer codes. If you can't get a more specific code, 400 Bad Request with an expressive payload is useful. The 500 codes are generally transport layer.
The reason that APIs are getting easier and easier to understand and use is because we're using the same design patterns consistently and repeatedly. Therefore, the understanding you gain from the Twilio API can be applied to Stripe. If you use existing tools in new and "innovative" ways that are contrary to - instead of in addition to - to their intention, you're setting back adoption and making your users re-figure out basic things. Don't.
Or worse, people don't realize how you're misusing the tools and build flawed systems.
(The one exception I'd give you is 202 Accepted which is generally used for "we've accepted this for now but processing and final validation may occur later" - it's a tentative success message.)