Safety is relative. Null can be just as deadly as Low.
However, when you are attempting to run sites (or missions), Low Sec is probably the riskiest place to do it. Maybe Wormhole space is riskier, but it’s harder to find a good variety of sites to do. If I recall correctly, Low Sec also has the lowest number of systems (of the securities) which means that the same number of players can saturate the area easier. The higher population density also leads to more conflict. I’m not saying this happens across the entirety of Low Sec, but that it can happen without the aid of corps organizing something specific.
When trying to determine rewards, I always want to reward risk and effort. Our team hasn’t done the best job at it so far, but we’re learning and I think we’re getting better at it.