Since this a comic, let’s start with visuals. They are the part that will catch everyone’s attention and it also means that you can give the artist something to work on. This means that you need to make a lot of minor decisions that are going to add up quickly. So let’s go through those decisions.
Era: This is one of the two most important decisions to make right off the bat. An era is defined by a combination of its time, location, and moral outlook. When you decide to emulate the era, you are making a decision as to what people will be dressing , what the architecture will look like, and what beliefs are common among the people of your comic. Examples of decent eras are the Meijing Era of Japan, the Victorian Era of England, and the Pre-Civil War Era of the South. See how each of those phrases evoked a mood just by mentioning them? You can also define your own era, so just you know what makes it work.
You need to decide which era you are attempting to emulate, even if it’s a combination of eras. The era will define what technology is available, at least in a general sense. It also tends to define the clothing and other stylistic traits. You also need to debate how closely you will follow the era; a historical fiction will follow the era closely, whereas a more magical setting may not follow the era more than accepting its basic. Of special note is “indeterminate tech”, which is ostensibly a medieval setting, but high technology seems to be easily accessible if you know where to look, such as laser rifle disguised as a musket or even some sort of sensing device.
Geography: You have two basic choices here: The first choice is that the entire comic happens in roughly the same kind of geography, such as rolling, forested hills, or a huge desert, or even a large city. This is great if you are making some sort of point about ecology or just want a simpler geography to deal with. At the other extreme is a more realistic geography, which is one that has a number of different zones, such as mountains here, desert there, even some forest and plains; it’s just more interesting, but harder to draw. Keep in mind that even space has its own geography, ranging from asteroid belts to dead space to areas full of plasma.
You can also be a lot more exotic, such as a planet that is a whole tree to one that is a broken up bits of land. Your planet can even be a living being or nothing but sea with maybe a few islands. Have fun with the geography, but be advised that you need to know what makes it special from the beginning with an option explain why it it is the way it is. Just remember to be consistent and you can have all of the fun you want.
These should be two of the first things you worry about. But they are just the first…