After a while, any setting can grow stale, especially if most of your scenes take place in the same kind of place. Variety adds interest, and can make an ordinary scene stand out as something special. Try and think of different places in the region(s) of your comic. For instance, what kind of districts are there in your city? What might you find there? Maybe there’s a Chinatown district, or something more uncommon like an old-world Dutch district. Maybe your city was primarily settled by French immigrants, and there are a couple blocks that are still historical leftovers of that time. Even if your story takes place all in one office building, at least move from cubicle to cubicle, to the break room, to a restroom, to different hallways—something–to keep the story from being two talking heads with an unchanging backdrop.
If your story is more globetrotting in nature, you have a huge advantage. You can literally send your characters anywhere in the world to find the perfect locations for all your major scenes. After all, nothing says “quaint Spanish cantina” like an actual Spanish cantina. Creating a world from scratch? Go nuts, but remember that your world should be as diverse as our own. Start by asking what sort of feeling you want your regions to have, then think about real-world places that have that same feeling, and see what you can borrow.
Even within the same issue within the same city we bring the main cast of The Uniques to six separate locations, and this is just three of them. Push your work, never let anything get stale. Variety is the spice of life! (The Uniques by Comfort and Adam)
Artistically, you’ll want to use more than just background drawings to change the feeling of locations from scene to scene. Use the entire color palette to your advantage: vivid red sunsets; bright golden sunrises; deep green, hazy rainstorms; and cool blue night shots. White marble buildings, red and orange brick, red cobblestone roads, and black horse-drawn carriages. You can use all of these variable details to make each scene stand out on its own, or to give each location a unique feel that sets it apart from all the rest in the comic. You can do similar things with zipatone, by adding light, shadow, and mood to your artwork.
Not only does location make a big difference, but using color to change up the time of day can help to break up the monotony of a comic. (Rainbow in the Dark by Comfort and Adam)