In a letter it is essential to open with the appellation, or form of address, honouring the rank and position of the recipient:

Ambassadors: Excellency
Cardinals: Most Reverend Eminence
MPs: Honourable (Hon.)
Ministers: Honourable Minister (same for lady Ministers)
Apostolic Nuncio: Most Reverend Excellency
Pope: His Holiness, Holy Father
President of the Republic: Mr President
Prince and Grand Master of S.M.O.M.: Most Eminent Highness
Royals: Highness (Royal Highness/Serene Highness…)
Bishop/Archbishop: Most Reverend Excellency

Take care with the variations that the appellation may undergo at the time of writing the recipient’s address, whose function should also be specified (e.g. Ambassador):

Ambassadors: Excellency Mr. xy, Ambassador (of Republic of) …
Cardinals: Most Reverend Eminence xy, Prefect of Congregation…
MPs: Honourable xy, Chamber of Deputies.
Ministers: Honourable Minister xy, Ministry of…
Apostolic Nuncio: S.E.R. (Most Reverend Excellency) Mons. xy, Apostolic Nuncio
Pope: His Holiness
President of Republic: (His) Excellency xy, President of the Republic
Prince and Grand Master of S.M.O.M.: Most Eminent Highness xy, Prince and Grand Master of S.M.O.M
Royals: His Royal Highness xy, Prince of…
Bishop/Archbishop: S.E.R. (Most Reverend Excellency) Mons. xy, Bishop of…

If the personality possesses more than one title, only the highest title is used.