(or "The Eternal Struggle")
Captain America has had many storytelling engines over his long, long career as a super-hero. He's been a soldier, an Avenger, an agent of SHIELD, and even a uniformed policeman (he seems to gravitate to authority figures, for some reason.) But you'd probably be forgiven for thinking his storytelling engine is "fighting the Red Skull"--in the first three volumes of the Essential Captain America alone, the Red Skull appears in over 25 issues, and even many of Cap's other foes, such as HYDRA or AIM, turn out to have connections to his arch-nemesis. (By Mark Gruenwald's time as writer of the series, the Red Skull turned out to be secretly bankrolling AIM, HYDRA, ULTIMATUM, the Scourge, and the United States Commission for Super-Human Activities. Now that's a Type A personality.) Even now, current Cap scribe Ed Brubaker is doing another Red Skull epic; Cap seems to be a superfluous element in his own book, next to the struggle against the Nazi tyrant.
So why is it that Cap and the Red Skull seem doomed to battle forever? And just what is it that makes the Red Skull such an enduring foe?
To answer the first question, you just need to take a look at Captain America's origin. Not the super-soldier formula, but his origin as a patriotic hero during an era when patriotic heroes worked best--World War II. Cap's Golden Age adventures were all as the star-spangled hero of World War II, and the sheer iconic power of the Nazis as "global villains" continues to make them menacing bad guys even today. (And as an aside, it's interesting the way Marvel and DC took two different approaches to World War II in their fictional universe; DC kept its heroes out of the war via the plot conceit of the "Spear of Destiny", making it a war fought strictly between humans, while Marvel gave both sides super-powered soldiers, turning "supers" into another theater of combat alongside air, land and sea.) If you look at Cap's other enduring villains, they're pretty much all former Nazis as well--Baron Zemo (I and II), Arnim Zola, and HYDRA and AIM can both trace their ancestry to Nick Fury's Nazi sparring partner, Baron von Strucker. The Red Skull just happens to be the best of these old bad guys.
So what makes the Red Skull the best? Here's a few guesses as to what makes him an A-list villain. (And not just him, either. Many of the best villains share certain traits.)
For starters, he's someone who has a lot, but wants more. You never see the Red Skull robbing a bank, or knocking over a liquor store. He's always got the funding and resources to equip a small army, own an island lair, build and bury giant Nazi robots for later use, et cetera et cetera. (Doom and Luthor are two more good examples here. When Doom loses, he's still in charge of a whole freaking country.)
Second, he's got lofty goals. He doesn't just want to be rich, or impress women, or avenge some slight against him--he wants to topple the governments of the world, send human civilization spiraling into chaos, and then set up a tyrannical dictatorship in the sprawling ruins. (Again, you can point to a lot of great villains here. Magneto wants to bring about a new utopia of homo superior, standing on the ashes of the human race.)
Third, when his plans fail (as they always do for every villain), the Red Skull doesn't wind up slinking off to jail with the henchmen. No, this is a villain who does things dramatically--escape via rocket-powered jetcraft, lost from view when his island lair blows up in a volcanic eruption...heck, even his seeming deaths are dramatic, such as being trapped in the brain of a renegade Russian general. He may escape, or may meet a seeming end, but he never truly has to face justice for his crimes. (Likewise, you'll never see a villain like Darkseid doing three consecutive life terms for attempted conquest of Earth.)
It does seem that the Red Skull is truly an evergreen villain, one who will continue to struggle with Captain America for as long as there is a Captain America (and even longer, if Marvel's heartfelt protests about Cap being really really really dead this time are to be believed.) It's difficult to create a villain that good. Certainly Cap would have had problems if Batroc the Leaper was his arch-enemy all these years.