Here's #25! Click here for the master list!
Captain America #25
The concept of the twenty-fifth issue of a comic being special is a relatively recent one, and the decade in which this idea particularly flourished, the 1990s, was not exactly a great time for big comic book issues (with notable exceptions, of course).
Surprisingly, though, the most notable twenty-fifth issue that I can think of happened in the current decade, with last year's Captain America #25, which featured the death of Steve Rogers, the original Captain America.
What is particularly unique about this comic, outside of the excellent artwork of Steve Epting and the strong story by writer Ed Brubaker, is the fact that this issue, the death of one of the biggest characters in all of comics, is part ONE of a storyline!
That alone let you know this death was not your usual attention-getting case of a character being killed.
The media attention of this issue was quite impressive, a lot more, I think, than anyone expected, as how could Captain America's death be considered that big of a deal when Superman was killed 15 years earlier? However, people apparently DID care, and that whole minor stuff about the Vice President was considered small news compared to the death of Steve Rogers!
It did not hurt that the comic was, in many ways, the finale to Civil War, one of the biggest superhero crossovers ever.
Other notable 25th issues include X-Men #25, where Wolverine loses his adamantium skeleton, Whiz Comics #25, where Captain Marvel Jr. first appeared, Animal Man #25, the penultimate issue of Grant Morrison's tenure on the book, Saga of the Swamp Thing #25, the "first" appearance of John Constantine, Fantastic Four #25, with a notable Hulk/Thing fight by Kirby (when I asked some people, two people recommended FF #25 as their choice) and I'm sure a few other notable ones I'm missing (unlike those issues I'm intentionally missing, like Quasar #25, where Quasar gets a new costume, that lasted until his death!).