I like the idea of having clues in the runes. Because they're only clues, they're not a vital part of the game and are optional. The runes provided small hints in Divine Divinity, although nothing you couldn't work out in an instant. Perhaps if the treasure maps or secret areas were hidden by runes. You could even have a magical vault where you a told the word that opens it, but you have to spell it out in runes.
Some people want a bit more thinking in their RPGs, and this is an excellent way to implement it without putting off the hack-and-slashers.
Also, learning an alphabet for a game isn't too difficult. Riven and Exile had new alphabets and number systems as required puzzles and many people got through those games. Enough clues were provided to teach people the language.
