One little trick I've found helpful is this:
Stagger your panels.
The basic idea is to never have your gutters (or panel borders) form a "+"
Instead, offset it a little. I do it all the time.
|There's a big and a small off-set on this page.|
Exception: When you have material that can (should?) be read in any order.
Doing this one simple thing and playing with it will help your readers know how to read your comic without thinking about it! Then they can get caught up in the characters and story.
Now go make some comics!
EDIT: There is one other exception that I neglected to mention: if you make your pages all with the same layout consistently through the comic, it can be okay to just establish reading order as a matter of habit. However, I still think that can be unnatural and jarring for a reader if they aren't used to your comic pages yet.
Also, comic strips combined into a book don't count because there is a much larger horizontal space above and/or below each strip. In the above suggestions, I'm referring to (1) entire pages (2) with similar gutter width between all the panels.