My brother passed away at the age of 23 because of a design choice in a video game. As an epileptic, especially one who had photo-sensitive seizures in the past, he knew that gaming carried with it a risk; but that risk was exacerbated by someone wanting a strobe effect here or a flashing explosion there.
Epileptics and their families know that activities like driving, swimming, or even crossing the street are made more dangerous by the sudden randomness of seizures. I don't lay the responsibility of my brother's death on a single game developer's door, but I can't help but wonder if they had even considered the impact a lighting effect could have on someone's life.
The same year of my brother's death, my housemate was a young college student who was also legally blind. She had an entire infrastructure of book scanners, screen magnifiers, and a special keyboard and mouse to help her with her work; but she still had to ask for help with simple things like finding the login link to a textbook vendor's learning management system. Understanding a course syllabus, filling out timed online quizzes, turning in homework, or collaborating in course forums took so much extra time that she took an extra year to graduate because she couldn't possibly take a full course load in a semester and keep up.
Technology in general, and the web specifically, has enabled people with disabilities to do today what was either extremely difficult or even impossible twenty years ago. However, a gulf still between these users's experiences and what we as the designers and builders of the web assume is the way our projects will be perceived.
Web sites are now expected to work on a wide array of devices and screen resolutions, but somehow screen readers and magnifiers are never listed as a "device" when speaking about responsive design. Developers are working on touch-friendly interfaces, when we still have web applications that are not accessible to someone using only a keyboard, or using foot pedals as a pointing device.
Making sure your single-page web application has proper ARIA roles, or ensuring link text makes sense out of context will make a set of your users extremely grateful and happy. I think that's probably more impactful than fine-tuning device break points or A/B testing the shade of green on your homepage. The decisions we make have profound affects on the lives of others, the difference between graduating in four years or five years, the difference even between life and death.