In my opinion CS5 has been the most significant upgrade in AE history only because of 64bit, it just makes a world of difference to have access to more than 3GB, the max the 32bit OS gave access to as far as i remember.
And as far i am concerned CS4 was the most unreliable version of AE, it crashed all the time, almost always because of ram limitations. And that was a dark period of AE, since most other versions had been so stable, going all the way back to v4.1 :-)
CS6 was also a mayor release feature wise and the new cache is really a timesaver. Yes, there is a few gotchas with it, especially with thirdparty plugins, but make sure you have the latest updates from Adobe and the plugins to see if they might be fixed by now.