A terrible affliction spreads through the land: A disease, highly contagious, which makes its victims mildly ill, but then permanently paralyzes the vocal cords. Dozens of reputed cures and protections are sold in the marketplaces, which gradually grow quieter and quieter...
Not every prophecy needs to be meaningful to effect a game. In the Lord Dunsany play, The Golden Doom, a child's scrawl has an entire kingdom struggling to puzzle out what sinister prophecy it portends.
The Wizard-Brewers of the Old Empire stored memories in bottles of mead, passing their brightest ideas, most subtle magics, and most important decisions on to their heirs in bottles of oddly-flavored honey-wine. A cache of these ancient magical vintages has been unearthed, but does anyone dare drink from it? The ancient mead's creator is a complete mystery, as are the thoughts he left behind.
What if the sources of precious metal in the realm all failed, so that the only sources for gold and other precious metal were hostile foreign lands? Gold coinage might become increasingly rare, resulting in hoarding. Player characters that appear with masses of treasure might be suspected of being in the pay of foreign powers.
The villages around the capital have a strange new disease cropping up. Spread by a fungus (much like ergot poisoning), it causes its victims to be very sensitive to sunlight. Hundreds of peasants are hiding from the sun, only coming out in the darkness to labor in the fields. Unfortunately, rumor makes their behavior sound more sinister and secretive than it really is.
Jemas Lorne, the most celebrated poet of the age, was found dead, clutching a fragment of verse torn from his journal. The tantalizing fragment spoke of wealth:
Golden sands, empty and cold,
Treasure's crypt, forgotten gold.
Under stone, ancestor's doom,
Noble's prize, troubadour's tomb.
Rumours claim that the poet's father, an eccentric nobleman, had hidden much of his wealth before his death. Perhaps the missing journal has more clues?
The player characters, experienced and somewhat well known, hear rumors and travelers' tales about a distant area being overrun by dragons (or other terrifying monstrosities). The locals have sent them a message, begging for heroic aid.
When they investigate, they discover that nothing of the sort is going on. It turns out that a group of thieves wanted them out of the way so that they could rob them (or someone who would normally receive their protection).
Near a major city, a mirror image of the place has appeared. This strange double is infested with hostile insectoid humanoids that appear to match the city folk in numbers and armaments. The humans’ diviners have determined that the secret of the city’s appearance can be found within the double’s college of magic, so heroes are needed to explore within this mirror city and discover what has drawn it from its distant realm. There isn’t much time to spare, as the bug folk find their mammalian counterparts unnatural and blasphemous, and plan to destroy them.
Nearly every primitive culture has had rituals and celebrations to guarantee the proper passage of the seasons and to ensure the fertility of crops and animals. Oversight of these ceremonies was generally the provenance of local kings or priests.
Suppose that the adventurers dispatch one of these fellows. The local peasants may become hysterical, fearing famine and death will stalk the land. Alternatively, they may want one of the new heroes to become king. For a while, this can be a good thing, but the first time that the crops fail, the superstitious locals will want to sacrifice their new leader.
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...