"I will go down with this Ship
—Dido, "White Flag"
The One True Pairing (usually abbreviated as OTP, not to be confused with any of the other OTPs or 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 One True Pairings 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".
One True Pairing Shipping Wars are second only to Subbing Versus Dubbing for heat and violence. The degree of fanaticism displayed for a particular One True Pairing 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 One True Pairing 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 One True Pairing.
It is technically possible for a person to have multiple One True Pairings, even in the same fandom.
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.
The opposite phenomenon is the NOTP, when fans have a pairing that they absolutely despise. While in many cases the NOTP is because of shipping reasons (as in absolutely hating the rival ship to their OTP), there are many fans that state that they do like the characters individually but absolutely dislike the ship for other reasons (don't liking the dynamic between the characters, disliking the way the creators handled it if it is a canon pairing, hating the Fanon the ship has accumulated, etc.). Their presence on shipping wars only make them even more bloody.
Often the term "OTP" is used sarcastically in parody of shipping, especially if it involves an unconventional pairing, or a character and their favorite food ("Hiro/Waffles OTP"), or (in a sightly less sarcastic bent) "Woobie/Happiness OTP" etc etc.