Mail looks like the worst business in the game: even if I put mail stops connected with the biggest factories (high level of mailing) the amount of the mail delivered is ridicolous and the loss enormous; does anybody know how to make a profitable mail business? It's the only one that seems impossible to make money with...
Mail is different from other goods, similar to p****engers. Usually just a point-to-point connection does not work for these two - you need an extensive network that allows people from more or less all houses in a major citiy, to reach more or less all houses in other major cities. In other words: just make sure that the coverage area of your p****enger network's (including small local bus or tram lines) stops cover most of the area of your cities.
Mail should follow the same principle - just in smaller numbers.
INdeed you need a extensive network, similar as for p****engers but with much smaller numbers: The amount of mail generated is about 1/3-1/4 of the same number of p****engers (with the exeption of attractions, that should put 8x more mail outward than inward).