Like on a giant's head or a dragon's back (or a pixie on a human's back)...are there rules/penalties/bonuses regarding such a thing?

I think it would be like fighting on rough terrain, with rolls varying according to skin condition and movement.

See shadow of the colossus?

Entirely up to your GM's personal ideas on how it should work.

As seen here: http://www.shamusyoung.com/twentysidedtale/?p=1235

Off the top of my head:

• Close combat hits are twice as likely. i.e. add 10 to your attack bonus
  
• Point blank range missile attacks miss only on a natural 1, re: surfin' Legolas
  
• A natural 20 on the creature does these things:
  
  • Spine - monster makes a Fortitude save or is paralyzed.
    
  • Head - monster makes a Fortitude save or is confused until it's next turn. Then it makes another Fortitude save, and so on, until it's no longer confused.

I haven't really factored in monster/character size ratios here, but this is how I'd run it if I were DMing, your monster-mashing may vary.
This message was last edited by the user at 18:25, Sat 07 June 2014.

Also - eyeball gouging!

These are just normal attacks, but naturally cause problems for our beleaguered beast. First (or first 50% of eyes for multi-eyed monsters) causes confusion. Second (or all eyes) causes blindness.

Bear in mind, the fluid from a bursting eyeball can be rather icky, so Legolas would be rather squeamish in such an event.