Definitely. I'd actually go one step further and say that they will eventually lose a crew of astronauts. Perhaps to the ISS, but most definitely to Mars. The Falcon is the most reliable rocket ever made with some 335 successes for 2 failures contrasted against e.g. 133 and 2 for the Space Shuttle, but that failure rate is still extremely high relative to something like an airplane. And the overwhelming majority of all space flights are for "simple" repetitive tasks. As we increase the number of manned missions, as well as their complexity - the eventual loss of crewed missions is an absolute certainty. Something like 3% of all astronauts have died 'on the job' making it likely the single most dangerous profession in existence. Space remains extremely complex and dangerous, and it's likely to only become even more so in the decades to come as we increase the complexity of tasks carried out.

The reason NASA's failures were such a huge deal is because they shouldn't have happened. In both cases you had issues with the managerial layer ignoring the engineering layer, and moving ahead in high risk scenarios - that was particularly stupid in Challenger, where they also had a high profile civilian aboard. In SpaceX the managerial layer and the technical layer are largely the same thing, and they also have a system where any flight engineer can independently cancel a flight, for any reason, at his own discretion. So the chances of a flight moving forward with a predictable risk is quite low. So what will most likely happen when they lose a crewed flight is an investigation to ensure it was not caused by systemic errors, some effort to ensure that whatever did happen does not happen again, and then a return to flight.