Return of the Obra Dinn looks like a fairly primitive game visually but this is an illusion. The behind-the-scenes technical requirements are not inconsiderable. On modern systems, this is (hopefully) well hidden by a high, smooth framerate. On older systems, lower inconsistent frame rates may lead to motion sickness, fatigue, and discomfort.
If you're feeling visual discomfort while playing the game here are some things to try:
1. Use one of the "Sharp" or "Sharp X" output modes
The "Smooth" output mode adds several full-screen filtering effects that may negatively impact the framerate on older systems. The "Sharp" output modes are direct 1-bit output and generally less costly performance-wise.
If available, the framed "Sharp" output modes can also improve visual comfort by reducing the window size and making the high-contrast pixels smaller and easier on your eyes.
2. Change the monitor type
Experiment with the "Monitor" setting to change the colors displayed for on and off pixels. Some of the options have lower contrast and can be more comfortable.
3. Force the game to run at 30fps
By default, Obra Dinn tries to run at a smooth 60 frames per second. If your computer can't play it at this framerate, then you may experience uncomfortable hitching or stuttering while playing. If that's happening, try running the game with the "30fps" command-line parameter as detailed here. Older systems are more likely to hit a constant 30 frames per second or better, and a smooth framerate is often desirable to one that oscillates between fast and slow.