don’t know if you ask just for sites or if you are thinking about building a site. in second case - hmm, I say you should define a bit better WHAT do you want to SERVE for your 50,000+ visitors.
means: when your server/cluster goes easy with a native php/mysql solution - CI can do it (nearly) as fast or even better with a clever .htaccess-modified caching.
check CI’s code - just a frontcontroller, some decorators - really thousand ways to improve performance coz YOU control the code - not the framework as smetimes felt in rails, symphony or cake. run some ab performance test against some activerecord queries ... the “view” in the CI mvC is lightweigthed PHP solution - bleeding fast (no smarty-headaches 