There are only a few settings that can't be configured via .ini files (the Widescreen hack is one? I think it is up for being added soon if not). But no, not every .ini file is "perfectly" pre-configured to every user's needs.
That thread is exactly what you're looking for. Want to set AF to 1x in SMS and turn off Texture Filtering? Edit the game's .ini file. Want to mess around with VSync in F-Zero? Edit the game's .ini file. The .ini files are there so you can have custom settings fit for your needs for each game, especially for front-ends where you can't (and really shouldn't) have to fiddle around manually with the settings before playing.
Now, how to get those "perfect" settings in the first place? Mostly a combination of reading the wiki and trial and error.
That thread is exactly what you're looking for. Want to set AF to 1x in SMS and turn off Texture Filtering? Edit the game's .ini file. Want to mess around with VSync in F-Zero? Edit the game's .ini file. The .ini files are there so you can have custom settings fit for your needs for each game, especially for front-ends where you can't (and really shouldn't) have to fiddle around manually with the settings before playing.
Now, how to get those "perfect" settings in the first place? Mostly a combination of reading the wiki and trial and error.