In this new post, Mike Wallner talks about making the move up from his PHP 4.4 environment straight up to PHP 5.2.
Anyway the only issue I really had, in spite testing the code really well over time, was with class_exists() and millions of warnings because of a missing __autoload().
The problem for him was caused by a combination of the new default behavior of the class_exists function and the autoload not included. He does note, thought, that APC works well with the new installation, though (and uses less memory).