Set this in .s3cfg:
host_bucket = %(bucket)s.s3.AMAZONAWS.com

s3cmd ls s3://somebucket
ERROR: S3 error: 403 (SignatureDoesNotMatch): The request signature we calculated does not match the signature you provided. Check your key and signing method.

This used to work in 1.6.1. It's a new issue in 2.0.0.
It appears 2.0.0 has changed to emit the Host header in lowercase conversion. But the signature was computed with the original hostname without conversion.