After quite a bit of in-depth investigation by our engineering teams, it looks like the vast majority of issues with 4xx errors were the result of client-side problems.
As you may remember, we [node:17585, title=“announced deprecation of HTTP 1.0”] back in May 2013 and have posted several reminders since then. A recent backend update more strictly enforces the HTTP 1.1 standard (http://www.w3.org/Protocols/rfc2616/rfc2616.html), which is partially responsible for some of the 4xx problems posted about here.
For those developers using Phirehose (https://github.com/fennb/phirehose), we strongly recommend updating to the lastest version, which is reported to be HTTP 1.1 compliant and fully compatible with Site Streams. (For those not married to PHP, you may consider HBC (https://github.com/twitter/hbc), an open-source client that Twitter maintains.)