"Tu lis une lettre ?"
If "Tu lis une lettre?" is "Do you read a letter?", inquisitive, what would be "You read a letter", declarative?
Put otherwise, what, if anything, indicates that this is a question, besides punctuation and inflection?
Nothing. Punctuation and inflection (and context in some cases) would be the determinant for whether it's a question or an affirmation.
I believe it is just knowing that it's Tu lis, je lis, il lit, elle lit type of thing. I can't hear any difference.