Imagine a tribe of nomads where all the males have the blessing of being were-stallions. The tribe would not need to have ordinary horses to move around, all mounted warriors would be female and a curious custom could be that when a couple gets married, the girl rides her chosen to the altar.
A character who is undergoing changes of personality (like buying off mental disadvantages - flaws - or changing alignment) might confront personifications of aspects of his personality in dreams: a griffon representing the courage he needs to face a terrible foe, or a satyr standing for the lecherousness a warrior must overcome to be admitted to an order of knights who must uphold vows of chastity.
If mana recovered slowly enough, and mages could pass it on freely between them, the ephemeral force would become a valuable trading commodity on its own.
What if a mage passes his powers on to his firstborn son, and a female mage to her first daughter, leaving the parent POWERLESS? A plain mortal, a sorcerer no longer, all wizardly might gone?
Or: what if a female wizard recieves the power of a mage who sires a child with her? Could lead to promiscuous witches and overly careful mages.
What if cancer is not an ailment if one has a will powerful enough, and knows what do do. What if one using the right techniques could control it and use it to become immortal, or to grow into something else?
Pick up a pathology/microbiology book, and add the diseases/syndroms to your game. Your players will freak out.
Coughed at? Diphteria. or tuberculosis?
Drunk from a muddy stream? Or just walked through? Well, let us introduce you to schistosomiasis...
Hit by a stream of energy? Too moch mana is ust like too much radioactivity - perhaps all mages could develop cancer early if too powerful...
Animals have parasites and diseases, so do plants, there are even bacteria that cann dissolve oil spills or plastic or what have you - why couldn't there be a disease living off magic - a magic item could be infected, losing power and speading the plague to other equipment it contacts, while a magic user would slowly lose his powers and contaminate all he works with or casts a spell at...
Whilst exploring underground the PCs discover tube like tunnels stretching for miles, upon further inspection the strange tunnels seem to connect all major cities in the are, what is their purpose?