Whenever the PCs come across an uncharted river, roll d20 on this chart (or d100 for a more mundane setting).
1: Holy. This river flows from a sacred spring and actually runs with holy water. It might be a magical forest brook or it might be a major trade river, with fervently religious cities on its bank, hordes of pilgrims rafting down its water, and holy-water bottlers and distributors driving ritualist clerics out of business.
2: Deep. Whatever its width, this river is so deep that it’s navigable by sea-going warships. In fact, its depth is unplumbed. It’s rumored to go all the way down to the Plane of Water. Every once in a while, bizarre sea monsters surface, snatch a ship, and disappear.
3: Magical border. One side of the river is reasonably civilized, with the occasional village and farmhouse along its bank. The other is monster-haunted wilderness, from which blood-curdling howls can be heard at night. How is it that such a long, meandering, un-patrolled border can hold back the forces of evil? It’s because these monsters can’t cross running water (they’re vampires, witches, or other such creatures) or because the other side of the river is the borderland of another plane (faerie or Ravenloft for instance).
4: Fertile. The farmland around this river is incredibly economically important. Like the Nile, it can support an unusually dense population and produce enough excess food to sustain the rest of the kingdom. Possession of such a river is worth warring for.
5: Not water. Blood, wine, mist, lava, mercury, acid, liquid sunlight, potion of delusion, stars, sighs, dreams – whatever it is, you can build a bridge over it and you might be able to sail on it (although you might need a magical boat).
6: Roll d6 twice more on this chart.
7+: Just a river.
Edit: Check out the comments for some more good ones!