You've got:
1.) The Awakened Threat - Cthulhu, Ancient Dragons, Primordials, etc.... can awake and need to be addressed. To me, this is a bit of a cheat as you're often bringing the Planes to the Prime to make this happen, with the threat(s) being extraplanar in origin.
2.) War - A massive war between nations can be more than a backdrop for a high level adventure - navigating the war and finding a way to end it can be a high level campaign. I ran a campaign where there was a lot of pressure building for two massive nations to go to war throughout the campaign and they finally did around the times the PCs reached 15th level. The campaign essentially ended with a massive 24 hour (real time) battle scenario taking place over 6 sessions with the actions of the PCs in this battle shaping my campaign world's entire future.
3.) Go Small - If your players are more RP focused, the high level adventures do not need to be about power, but can be entirely about story. Think about the stories where "All the Power in the World will not help you now..." I had a campaign where a Trickster God was the BBEG for the tail end of the campaign - and he used his power to make the PCs choose between saving and protecting those they cared about, or trying to stop him. They elected to save those they swore to protect. However, even in those things, the Trickster made sure the PCs would lose (or tried to do so) by making sure the threats they had to face would require personal costs. It was a more ... intimate ... and psychological end to the campaign.
4.) Time Travel - You need to prepare and think about how you want to do this, but you can send PCs to the future or past and massively change your campaign world around them to give them a world that is more dangerous and appropriate for high level play. I've sent PCs to Gamma World, the ancient era of the Primordials, and a Sci-Fi Fascist Utopia ....
5.) Deep Beneath the Earth - My campain setting's prime world is about 12 times the size of Earth - on the surface. About 100 miiles beneath the surface is a Dyson Sphere style 'Underdark Surface' that surrounds a faint Purple 'Sun'. Inside that Sun is a place that PCs have adventured that is entirely my own creation with strange rules/dynamics (essentially, designed to be 4 dimensional to appease the science freaks in the group). Anyplace isolated far from the rest of your campaign world can be really strange - which can work for high level games.
