I have been running the same D&D campaign since 1992. We started under 2nd edition AD&D, but never really made the Skills & Powers changes. When 3E came out, we changed over, and are currently in the process of making some 3.5 updates. The rules changes we have made over the years haven't been a big deal, especially since I have always rather extensively house-ruled my games (hit locations, spellcasting rolls, 12 different spellcasting classes, cap at 6th level spells, etc).
As far as how I started the campaign, it was without an overriding plotline. Initially, it was letting the PCs explore, make new allies and enemies, and become more knowledgeable about the world. After they had some knowledge about the world and were around 3rd level, I began interjecting short plot arcs of 2-4 adventures dealing with similar themes or events. I didn't run the related adventures one after another though- I'd throw in unrelated adventures as well. After a few cycles of this, the PCs will have some strong likes/dislikes and will have developed interests of their own, and agendas they want to pursue. I developed my homebrew world as they went, adding on interesting bits here and there, fleshing out things as they encountered it, or as inspiration struck. I never made an uber-villain or over-arching theme, because when you do that, you suddenly place limits on your world.
Currently, the group is in the middle of a plot arc involving mortal agents of Asmodeus trying the bring the Arch-Devil back from oblivion after mortal followers of the paladin's church and the sun god's church summoned him and tried to fragment his spirit. While they believed he was destroyed, in fact his essence slipped into other spirits and the land, corrupting them, and his followers are attempting to re-assemble enough of his soul to bring him back. The PCs course isn't clear cut though- they may end up aiding the diabolists, since long ago the gods and demons decreed that they would not war with each other again- and the mortals who did this to Asmodeus broke that accord- incurring demonic wrath. Or they might fight against the diabolists, and risk another demonic incursion which would kill thousands of people. Or, most likely, they will do some rat-bastard sneaky thing I never expected and have some REAL fun.
There are a few things I think that are needed to run a long-term game.
1. The first thing you've got to have for a long-running game is friendship between the players outside the context of the game. Most of the people I have gamed with in this campaign were high school buddies, my sister, or people I met in college and invited to join after we were friends. We have had about a 50/50 split between men and women in the group, which I also think helps to keep perspectives fresh since it isn't just a bunch of guys getting rowdy and killing things.
2. Trust the DM. This one sounds like a no-brianer, but its vital. If players are always second-guessing the DM, his rulings, and what he allows in the game, the game won't make it very long. As the DM, you've got to be fair, know when to pull your punches, and when not to budge. I run a low-magic world, and when one character said he wanted a holy avenger sword (under 2E), I said such weapons don't exist in my world. He huffed and puffed for a while, but eventually acquired a sword that was used by one of the important saints of his religion- and conferred some of the traits the saint was renowned for on him. Not only was he happy with this, he preferred it to a holy avenger, even though the equivalent plus on the weapon in 3E is only +3. Be willing to work with your players to make them happy, but don't cave to them or give them exactly what they want.
3. Which brings me to this point- keep the players guessing. Never quantify something as a DM in a concrete manner for them. Don't ever tell them they are attacked by 4 trolls- describe the trolls, but don't call them by name. Come up with new and unusual situations, opponents, and even allies. I have learned to NEVER absolutely state another character's alignment- let them wonder about the NPC, his motivation, ethics, etc. I also don't tell my players the exact plusses of their weapons, armor, etc. In fact, I still keep most of their stats a secret. Sure, they know that they are 10th level, but they don't know how many HP they have, how many are gone, what their exact saves are, their AC, etc. All of my players agree on this one- by keeping the focus off the numbers, their characters become more real to them, and they make decisions based off what happens in the game, rather than off min/maxing a situation. Obviously this one goes hand-in-hand with DM trust. It requires more work from the DM, but its worth it.
4. Let them see their actions have consequences, for good or ill. Most DMs gloss over this one- but I have on several occasions had repurcussions for events they were involved in YEARS previously in the campaign. Sometimes, the PCs have forgotten an important loose end that comes back, other times they might have a mysterious benefactor who profited from their actions offer assistance. Let them know the world is a dynamic place, and while they are important, the world doesn't center on them.
5. Allow the PCs to establish strong relationships with NPCs- then don't kill those NPCs off as plot hooks. This helps the players relate to the world on a personal level, rather than "we must save X because it is the Good thing to do." Foster friendships, rivalries, hatred, etc between specific PCs and NPCs, and bring back these NPCs occasionally. The guy who plays the paladin in my game actually teared up when his old buddy/friendly rival from his novice days in his church died. Believe me, it will suck the players into the world, and get them more motivated than a pile of gold or magic items ever would.
6. Give all your major NPCs complex motivations- not just alignments. I try with every semi-important NPC I create to list 5 positive and negative things about their personality, and give them a plausible motivation(s). This has resulted in some really unusual NPCs- for example: a self-righteous CG cleric who saw himself as the means by which he could bring down a corrupt government, but who was deeply afraid that others might find out that he was the major power involved in setting up the lord- so this he and his church might profit. Or a demonologist who tortured, experimented on, and mudered hundreds of souls to prevent his son from being ravaged by a disease that clerics and the nobility would not aid due to his low social station. Give NPCs real motivations, personalities, and beliefs- and the PCs will interact with them more than simply at the tip of a sword.
