As this site has a clear bias towards the anime version of Full Metal Alchemist (as there's just that much more Hughes in the anime), this is a rather quick run-through of his appearance in the manga (but the love, as always, is there). Be warned that there are the spoileriest of spoilers, so don't read if you don't want to know.
Hughes' first appearance in the manga version is in chapter six (found in volume two). He came to collect Tucker, but as all that Scar left of him was a corpse, there wasn't much point in having a trial. Hughes identified it as being Scar's work, and informs Roy about the serial killer they've got the loose. When a battle breaks out with Scar, Hughes goes into hiding until it ends, and shows no shame for it, claiming he's a normal guy and therefore won't be a part of their escapades.
Hughes then returns to Central City to get work done, and Edward goes to get his arm fixed, so after he sees Ed and Al off that's the last we see of Hughes until...
Chapter ten (volume three) when Ed and Al go to Central to research, at which point he learns of Seska's ability to remember any document that was contained within the burned down library, and steals her away for his own dark purposes. Well, truthfully he just has her copy down military records he needs for legal cases, but that doesn't sound nearly as dramatic.
The first glimpse of the relationship between Hughes and Roy is found in chapter fourteen (volume four) when he phones up his friend to brag about his daughter's upcoming third birthday, pass information to Roy about Scar, and tell Roy to hurry up and get married so Roy'll have another person to support him. When he's warned afterwards by one of the staff that if he keeps using the phone for personal use, he might get a pay cut, he says that his love cannot be stopped by things like that. Good old Hughes!
He then goes to visit Ed and Al (who are now hospitalized), and after making assumptions about Ed's relationship with Winry, who is also visiting the boys, he (literally) drags her to his house so she won't have to worry about finding an inn. After a brief stop for some shopping (as it is his daughter's birthday), they arrive at Hughes' house, where we get to see his family for the first time, and they instantly welcome Winry into their home (because they're just so damn nice like that).
During Elicia's birthday party, Hughes shows off the dad-side of his personality (though honestly, is he ever not in super-dad mode?), counselling Winry on her troubles with the Elric boys and pulling a gun when the little boys get too close to his little girl!
The next (and also sadly last...) chapter that he appears in is fifteen. Hughes discusses the events that have transpassed with the Elrics and Armstrong, which is interrupted when no one other than the President shows up, and warns them of the danger of what they're investigating and warns them to trust no one. But after seeing the Elrics off (again), Hughes of course goes back to his investigative work, and his hard work finally pays off. But Hughes' discovery doesn't go unnoticed, as Lust appears with the intention of killing Hughes, who knows too much. Hughes is part of the military, however, and not one to just lay down and die, so he fights back and manages to escape from her (albeit wounded).
Hughes knows he has to tell someone what he discovered, but as he doesn't trust the military phone-line he leaves the building in search of a pay phone. In his hurry to phone Roy, he drops a picture of his family, which is seen by someone who appears to be 2nd Lieutenant Ross, and who happens to have a gun aimed at Hughes. But Hughes isn't easily fooled, and realizes due to the lack of her characteristic mole that it isn't actually her, and goes to attack. But Ross who is really Envy is even harder to defeat than Hughes, and he turns into Hughes wife Gracia. Hughes can't kill his wife, but Envy has no problem with killing Hughes. When Roy finally picks up the phone, the line is dead.
The time we see Hughes in the Full Metal Alchemist manga is in the next chapter, when they lower his coffin into the ground.