For example, if I were to write Ore wa genki da, I'm using English letters to write a Japanese sentence - would the spell translate that (and would it make a difference if the caster didn't speak either language already)?
I would play this as if Comprehend Languages acted like Google Translate - it would pick up on all of the obvious and easily translatable words, but it would lose all context (there would be problems with pronouns, verb tenses, etc), and would occasionally be completely lost if a word was spelled too badly or couldn't be accurately described with the new alphabet.
Essentially, any information that was lost in the transliteration is completely gone and cannot be pieced back together by the spell. But enough data may come through for an intelligent person to use context clues to get the gist of what's going on.
Or, kind of like this:
http://www.youtube.com/watch?v=bpdeCdUC9r4