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.
A known immortal traveling with the PCs kills an attacker, and is arrested and charged with murder, since immortals cannot kill in self defense, being immortal.
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.
The PCs are accosted in a major city containing at least one famous fortuneteller / prophet of the future. They are informed that their as-yet-unborn child will (insert terrible evil), and that, although they are very sorry, the PC must be executed to keep this from happening.
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.
In ancient Rome, social appearance and respectability were everything. The most hated men were punished with damnatio memoriae, damnation of memory. Every trace that a person had ever lived was removed. Busts were shattered, freizes were marred, records were struck. Any sign of the hated figure was destroyed.
The heroes are travelling the great seas by ship. One night when the seas are calm and everything seems fine their vessel is eaten by a great whale. The end? No. They wake in the belly of the animal, it is like a great cave. Full of wrecked ships and strange things to be discovered. Will they make it out alive?
The members of the party has unknowingly been infected by a mysterious plague and have been spreading the virus for quite some time now while adventuring. They start to hear rumors of all the cities in quarantine after they travelled trough. Will they discover the source of this? Will people start to avoid them, try to kill them?
A city the heroes visit is in a crisis, the king and queen are getting a divorce. Who shall rule? The inhabitants of the city take sides by tying a red or blue ribbon to their swords, sticks etc. Whose side will the Pcs take?
A plague is spreading trough the lands, the plague is actually an old woman carrying a stick. She walks from farm to farm spreading the plague. Can the PCs stop her without getting infected.
What if dragon-sightings and evidence of such was treated with the same skepticism and mockery as modern UFO sightings? More for a low magic world where dragons 'dont' exist.
The PCs encounter a strange set of artistic drawings done on the ground as they pass through a city. It has been done in chalks and no one saw who did it. Wizards might recognize the writing within the colored square as an obscure and dead language with a message stating that a prominent wizard and a retired bard have discovered how to populate Arcadia with the spirits of the dead!
Is it a local hoax, or are the PCs crossing the path of a very deranged and possibly dangerous mage?
Enraged by the violation of the Peace Pool and the Whalebone Forest, a dead leviathan has risen from the bottom of the ocean and now hounds ships around the port where the stolen jewels went to land. It capsizes ships and devours sailors whole, spears protuding from its dead and crab-eaten hide.
Game Cliche 2.
Upon learning about "the five ancient jewels" or "the nine legendary icons" or whatever, you can be quite confident that Saving the World will require you to go out and find every last one of them.
Game Cliche 1.
All legends are 100% accurate. All rumors are entirely factual. All prophecies will come true, and not just someday but almost immediately.