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It really depends on what software you'll be using, but with a well configured server I don't think separate machines are necessary. You'd have to have either a shitload of traffic (thehun sized or something like that) or scripts that aren't supposed to handle lots of traffic.
Having a dedicated webserver for thumbs makes sense, as does splitting request across multiple subdomains, but you can do this on a single server as long as it has enough power to handle it.
So, unless MySQL or resource intensive PHP scripts eat up your CPU or I/O you could do something like this: Apache to deliver your regular website, on a second IP address Lighttpd or Apache (MPM worker instead of prefork) for thumb-delivery, possibly using multiple subdomains so your average browser makes more simultaneous request, MySQL chugging along in the background.
Todays server with something like 4-16 CPU cores and tons of RAM can handle quite a lot if you know what you're doing, but it really depends on what exactly you want to do.
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