I don't have a setup anywhere near that level, but I will recommend looking into two quad-port Intel NIC cards for networking. Squid depends a lot on how you configure it, what your users do, and how many do that. Keeping more objects in RAM is obvious, but with that many users I think you'll want a dedicated SSD for the squid on disk cache no matter how much RAM you have. If the usage is too heavy, you might want to consider a multi server setup using WCCP to coordinate the caches.