One True Pairing
"I will go down with this ShipI'm in love, and always will be"
And I won't put my hands up and surrender
There will be no white flag above my door
—Dido, "White Flag"
The One True Pairing (usually abbreviated as OTP, not to be confused with OOTP or OotP) is the couple that a fan or group of fans prefers over all other 'ships. Canon and logic do not necessarily apply, and Crossover OTPs are not uncommon.
The degrees to which this is taken varies wildly. It can mean anything from "I just like Drakken/Shego best" to "I won't read Fanfic that pairs Anya and Xander with anyone but each other" to "Cloud always and still loves Aerith and they made love to each other in the flower field at the end of the movie", to the extreme "All the canon evidence that Harry and Hermione are not going to get together is a lie spread by the Ron/Hermione 'shippers, who must be stopped before their evil destroys the universe".
OTP Shipping Wars are second only to Subbing Versus Dubbing for heat and violence. The degree of fanaticism displayed for a particular OTP may be proportional to their distance from the Official Couple and/or the Word of God for the work in question.
In some cases, holding their preferred characters to completely different standards than the official pairing is an excellent mark of OTP shippers. If someone argues that you need to show that X and Y got married to prove they're in love, and the rings on their fingers don't count, but they know that X and Z love each other because of 'chemistry', they're definitely defending their OTP.
It is technically possible for a person to have multiple OTPs.
Some people refer to their favourite threesome ship by the similar term One True Threesome, or OT3. Or really, "OT" appended with any number if they're even more ambitious with the number of people involved.