How exciting! I'm making a Keen4 mod myself, and I'll share with you my two cents about Sprites. 4 main things about a sprites, in my experience: Behavior and Collision, Height and Length, Design and Coloring, Animation and Movement. Actually that's 8 things.
For Behavior, I recommend looking at all the Keen 4 mods out there, like Zoltan's Revenge and Keys of Krodacia so that you can see what can be changed and how it effects the sprite. I also like to look at the unfinished XkyKeen4 mod, and Save the Quillsheep mod. Some cool creature patches in there. It's amazing what a few patches can do. You can change what 12 Inchworms spawn, or you can make the Skypest stunnable while it flies in the air.
One of the first spite replacements I worked on was one for the Poisen Slug. The first thing I noticed was the 2 frames -- the way one frame animates to the next. Since the Slug has only 2 frames for walking to the Right (and 2 for the Left), I decided to replace the Slug with an upright worm, which moves in a very similar fashion.
I'm really bad at drawing things from scratch, so I looked around to find something I could use as a guideline. Turns out Benny The Bookworm (from Word Rescue) was perfect! I erased his arms and umbrella, downsized him to fit the proper dimensions, and recolored him. Remember, you have a good deal of freedom as to how tall or short your sprites can be, but it's much more restricting how how long (length) your sprite is. Your Poison Slug could be as tall as a Council Member or as short as a Wormouth. This is what one of my work sheets look like:
It's extremely important to Save as you go. Whenever you're about to make a big change to your sprite, always remember to copy and paste it somewhere else first. That way if your work doesn't turn out right, you always have your previous version of the sprite to fall back on.
Since the Poison Slug releases that green poison puddle every now and then, I had to make Benny Bookworm do something similar. There was nothing left to do but make him constantly barf. So that's how poor Benny got to be the Barfworm.
When Keen touches the Poison Slug, he dies. But it wouldn't make sense for Keen to die if he touched the Barfworm. So I switched out the Slug collision with the Bounder collision. The result is the Barfworm pushes Keen around the level much like a Yorp. Keen can also ride on the Barfworm's head, but it still scoots along the ground like a Slug.
The Barfworm is in the top left corner of this pic:
It's really fun to mess around with sprites' collision. For instance, The Walking Tree you see in the picture above, is the replacement for the Berkeloid. The Walking Tree is no longer dangerous to touch, like the Berkeloid is, nor does it shoot fireballs. And the Bounder is now dangerous to touch but has the appearance of the Mad Mushroom.
So....yeah! Knowing what you can do with sprites in the way they interact with Keen (or in my case, Gramps), will affect the way your draw your sprites!