Should I Unset PHP variables in Drupal?
No, Drupal is not doing anything to handle this; the very fact you're asking might suggest you're not totally sure how this works, as Drupal has no power over the efficiency of the code you write.

GC runs every time a function finishes, so unless you've identified an actual problem in one specific function, clearing up every single variable after you've used it, even though you theoretically can, would surely be considered premature optimisation.

Bottom line: Drupal cannot help you to write efficient code, you need to apply what you know from PHP. Whether you want or need to free the memory for every single variable manually depends on your requirements and specific code. 

I would personally say you're over-thinking this a bit, as in an ideal world your functions should be small and modularised enough for this not to be an issue anyway. React to real problems, not perceived or potential ones, when it comes to optimisation.