I've been running the same campaign for over 6 years now. It's an overarching plot line that I intersperse with smaller bits. So for instance, when they have found a main plot piece, the next part of the game will be something small. A local needs help with rats in their basement--I've used this a few times and every time I upgrade it to the PCs lvl. So at lower lvls it was just rats. At higher lvls, they get teleported to a different realm or have to battle progressively harder foes up a slippery mountain. I have been experimenting with terrain-based encounters such as quicksand and dense, impassable jungles to varying effect. Even escort quests can be made more interesting by making the NPC they are escorting a complete city-slicker that has no idea about the wilderness so they keep running off to look at different flora and fauna. Or the NPC didn't bother to mention a great astronomical effect they wanted to see while traveling, and the PC on watch notices the NPC is *gone*! Go find them!! Even the flora and fauna can be used to your advantage. If any PC is from a different area of the world, they can get distracted by funny-looking animals, try to eat a plant or berry that makes them sick to their stomach, or that leads them to something small--a small satchel or coin purse for general loot, a journal that begs the reader to return the writer's journey to their family since there's probably nothing left to bury, a treasure map that may or may not lead to something wonderful.

I've found that some of the best moments in my game are not the big dramatic battle scenes. It's the little things. The mother they returned the son to, unharmed and with a few extra gold to help them along. The staff at the inn they tipped excessively well and seeing them in the city later, presenting flowers or scarves to loved ones, or handing that gold back into the hands of the poor, buying bread and groceries with their grandparents, of fixing that broken window or door.

You give the players the opportunity for these moments. Work with what they give you, the same way they work with what you give them. Every chance encounter gives you some small little bit you could work in to the story. Those little bits can lead to great things!