"This is your story."
A lot of DMs set their campaign in an existing videogame world in order to try to capture the feeling they had when playing it. The challenge is that you can't do that just by copying surface details like places and NPCs. You have to think hard about why FFX made you feel that way, and work out how to create a campaign that makes your players feel the same way.
Spira itself is actually an excellent setting for a D&D campaign. There's a clear campaign structure (the pilgrimage), a rationale for the party (the Summoner and her Guardians), a well-defined goal (defeat Sin), solid origin lore for creature types which map easily to existing D&D monsters (fiends = fiends, machina = constructs, sinspawn = aberrations, various humanoid types, unsent perhaps count as celestialssince they're essentially made of the same stuff as fiends, etc).
Here's my advice. Unredacted spoilers for FFX of course follow.
- You have to let your players create their own original characters in the world. Yuna isn't the only Summoner in Spira, even during her own pilgrimage. If your players haven't played FFX, they won't be familiar with the characters in order to play them. There's no point in making them DMPCs, because the characters won't have the same meaning the players that they do to you.
- On the other hand, if your players have played FFX, or watched a Lets Play of the game, the original game's plot twists won't hit like they did when you played the game. If you have them play the original characters too, then it's just fan character RP, which is fine, but it's not really a D&D campaign. Fundamentally, you can't railroad the players to recreate the story of FFX. You have to let the players make their own decisions and tell their own story.
- Accept that some of the plot points will not carry well. A major conceit of FFX is that Tidus, an outsider, is the only person in the world who doesn't know that Yuna is going to die at the end of the pilgrimage, and it only works that way because he never asks.
- It's somewhat acceptable to railroad the players from place to place, since FFX takes place across a pilgrimage between pre-determined spots, so the overall path is obvious. However, you have to let the players solve them in your own way. You don't have to stick to the exact route or timeline of FFX. You'll have to invent your own dungeons and puzzles for the temples, in particular, since they won't convert easily to a tabletop game.
- Disable raise dead. Aside from the fact that it doesn't canonically appear in FFX, it creates opportunities for the kind of bittersweet moments that define FFX's story. A Guardian sacrificing themself for the Summoner is absolutely appropriate to the lore. Even if the Summoner dies, you can still continue the campaign with another party, but make it clear that the party disbands when the Summoner is killed, being that the Guardians are defined by their bond to the Summoner. (It may be an interesting twist, if the players are really attached to their characters, to continue the campaign and have the Summoner come back, only to be revealed later as an Unsent.)
- Mechanically, there is no Summoner class in D&D 5e. Tasha's Cauldron of Everything has some summon spells, although they're spread across classes and not as powerful as the FFX ones. My suggestion is to make the Summoner a cleric (since Yuna is also a healer and a key party member), and give them unique summon spells of each spell level which can only be learned at each of the Temples, and which are always added to spells prepared. Be careful not to make them too powerful. You also can't enforce FFX's rule that the other party members suddenly vacate the field when a summon appears, since D&D doesn't work that way.
- Heavy armor isn't a major thing in Spira, probably due to the tropical climate. This is going to reduce AC for some classes.
- Consider how D&D's character classes will fit into Spira, and how Spira fits into D&D's rules. You'll need to prepare a document for your players advising them of the races and class options available. I suggest re-skinning existing races to fit Spira's species, perhaps adding a warlock patron equivalent for Sin, re-skinning existing monsters, etc.
The fundamental point I want to make is that D&D is a game of playing your own character and making your own choices. As Auron says to Tidus, "This is your story." You aren't going to evoke the same feelings as FFX just by leading players through the story. You can use the same setting as a backdrop, but from there you have to ask how to recreate the same feeling and tone.