Here's #48! Click here for the master list!
There actually are some fairly reasonable alternatives to this issue, but not really, as this issue features the introduction of Galactus and the Silver Surfer and is the first part of one of the most famous comic book stories ever (you know a story is big when it is adapted into a movie).
So it is definitely the top pick, as Stan Lee and Jack Kirby brought their game to a whole new level with this epic storyline (the issue itself is an odd one, as it first finishes the Inhuman storyline and THEN goes on to the Galactus story).
Remember the Justice League America story where they fight Despero? The first part of the story was also a split issue, with one half of the book being a wacky Spy Magazine parody and the other half being Despero killing people.
Power Man #48 was the first issue featuring Iron Fist, leading to the book changing its name with Power Man and Irom Fist #50.
Green Lantern (Vol. 2) #48 was the first part of Emerald Twilight and featured the debut of Kyle Rayner. I seriously contemplated using that instead of FF for a little bit, under the whole "not wanting to use the same comic for so many spots" theory, but I then discounted that theory as dumb, so Fantastic Four #48 had to be the pick.
Amazing Spider-Man #48 was a cheezy story with Vulture II.
The Sandman, Swamp Thing and Doom Patrol all had strong 48th issues.
Name me some other good #48s!!