If you've seen the movie Troy with Brad Pitt and Orlando Bloom, there is a scene as the city of Troy is falling where Orlando Bloom passes the Sword of Troy to a guy and tells him something to the effect of, "as long as this sword is in the hands of a Citizen of Troy there will always be a Troy" Something like that at least. At any rate, the campaign starts under similar circumstances and the Party consists of members of those escaping from the city as it is being invaded. First adventure consists of bringing the women, children, and elderly to safety. From there it could turn into a Kingdom building expedition as the party seeks to rebuild what they lost. Alternatively it could be a plot of revenge where the party seeks to liberate their former kingdom and stick it to those who have done them wrong.
2. Colonists in a new world
A very simple idea. Party arrives on a ship (or airship, dragons back, whatever) to a "new world" or perhaps an already colonized area similar to Xendrik in the Eberron setting, or Raven Rock in th Elder Scrolls Setting. The point is it's an outpost in a new land. The idea is to get the players out of there comfort zone and have them engage foreign monsters. If your party has spent years fighting orcs and goblins throw troglodytes and lizardfolk at them instead, or make up an entirely new race of monstrous humanoids.Perhaps they can establish relationships with the indigenous folk, learn new magics, and explore a vast new area. Try new environments like the Jungle or Desert, if they arrived by ship you can explore the coastline.
This idea came about after a botched attempt to run an Oriental Adventures themed game in the past. My group of players wasn't too keen on the idea of playing Asian themed characters, or rather I think there was a bit of a culture shock. Admittedly my approach was wrong, I handed them a document on Samurai etiquette and said, "Here you go!" and it was a difficult transition. Then this idea hit me, what if they were foreigners in an Asian setting. Think Tom Cruise in the Last Samurai or any number of Martial Arts movies where a Western Empire has a foothold in China or Japan. Rewind the timeline a bit (or not) so that everyone is using Medieval technologies and you're good to go. A similar concept could involve the Crusades and it introduces the party to a Middle Eastern setting and Culture. The idea is to let your characters learn about the setting through play and not force upon them this doctrine of unfamiliar etiquette. Having an NPC explain that the Samurai will likely kill you if you touch his Katana is better than having the player touch the katana and promptly start a fight with no explanation.
In a nutshell, Vanguard Bandits. The idea is they get magical (or clockwork) suits of armor that essentially polymorph them into large (or huge) sized Golems. This idea came about not only because I enjoy mecha anime, but also as a way to get players who'd rather play high level PCs back to level one. The compromise is, I give you a magical suit of awesome armor and you be level one again. I've never pitched this idea to my game group, but I've always kept in on the back burner. You can play around with how they get repairs and also the sizes of Dungeons to make the party enter or exit their mech suits as needed. Maybe there's a big heavy boulder in the way, you need your mech suit to lift it, but the passage beyond is too narrow to continue unless you dismount. As far as rules go, I envisioned an idea where you'd use the polymorph rules from 3.5 to let your players essentially take up the STR, DEX, and CON of the suit as well as some other qualities. Pathfinder vehicle rules might also work, but I think modifying the polymoprh rules might flow better in combat situations. Then again that might change if your mech suits are AT-STs or Gundams, choose a rule set that fits your concept.
The Assassin's Creed games painted a beautiful picture of Renaissance Italy. In addition I've always been excited to run a game in a Venice like city. Galantri from the Mystara setting is still one of my all time fantasy places to visit. Something about the boats I guess. In terms of technology though, the Renaissance period is an interesting one. You'd have more prevalent firearms and if that's not your groups cup of tea, certainly avoid this idea, but you can explore a Three Musketeers style campaign. Then again, you can explore any traditional campaign style, the point here is to play in a slightly more advanced time period.
It's Adventure Time! Simple premise. End of the World Scenario, but instead of Nukes in Modern Times (or the 1950s of the Future) it's Global Thermomagical Wizard War as them drop spells that blast civilization back to... well right where it is actually. Imagine though wasteland landscapes and horribly mutated magical creatures. Aberrations and Magical beasts will make up the bulk of your encounters here and the theme of the game is survival. Introducing a survival mechanic is a possibility and it rewards/punishes the party for not finding good sources of water, food, and shelter. Two alternatives here are the Rapture and Zombie Apocalypse. In the Rapture Scenario it's the end of days based on your campaigns religion. Maybe it's the actual rapture or it's Ragnarok, but the minions of Hell (or Helheim) are on the Material plane and they are looking to play. In the Zombie Apocalypse scenario, the zombie plague has spread across much of the known land and the players are just looking to survive. Smashing zombie after zombie gets a little boring however so I might expand this idea to include numerous undead types. This scenario could be focused around finding the cure or eradicating the necessary evil (it's probably a Lich)