I'm thinking that for the 'hero' you (do, in fact) need to use a loooong .png file (as it states here). Top row is for Right facing movements, 2nd row is for Left facing movements. BUUUUT, with character sprites of different sizes (when cycling through certain animations) the squared area can/will increase. So, I'm assuming you'll have to take the widest and tallest sprites/animation frames and make a box that fits those extremes. Then (maybe?) center each one (for instance, for when the hero is idle and not taking up much length and width) yet still aligning them to the 16x16 grid squares....?
I know I haven't been able to use this that much... With the game I'm wanting to (re)make I have over 120 different animations frames (er, make that) over 240 if I'm going to have to mirror almost everything for the 2nd/bottom row for left facing movements.
At any rate. For the 2 way horizontal (genre?) I don't see a way to make the hero be like a cat (go up hills ) e.g. tread up and down inclines.
The game? Strider. Ambitious? I'm thinking: Yeah.
Rastan would be out of the question too since it has slopes. Maybe a game like Black Tiger would be a more feasible project to undertake.
eta: I'm sure this 'slope' feature can be added later. It is still in it's early stages.