Have you (or anyone else) had a chance to A/B test caches? That is, setup network API requests to be duplicated/filtered from production and sent to test environment(s).. credit to netflix.
Setup enough identical boxes with each of Squid, Nginx, Varnish, trafficserver, etc. and evaluate each with basically the same traffic and however much tweaking.
Let's keep in mind that individual box performance will not directly translate into your cluster performance or global network performance. A box can be fine-tuned to serve a file at lightning speed, but once you connect a bunch of them together, and start delivering lots of different files to millions of people - different factors come into play. Distributing files, replacing files when updated, content churn, etc etc
Simple caching works for images, but doesn't work for large video files, for example (look at latest financials from public CDNs - they are all bleeding cash).
It's really not that simple as testing a box to see which setup works best.
Setup enough identical boxes with each of Squid, Nginx, Varnish, trafficserver, etc. and evaluate each with basically the same traffic and however much tweaking.