I would say they are...as said above, AIO units are sealed and, assuming you don't damage them, are as safe as an air-cooler. Have a look at the recent Tom's article on the $1.6k PC; the trouble they had with the NH-D14's weight (possibly) suggests that air cooling has its own risks. If you accidently nudge your PC tower, you won't dislodge a waterblock...you may cause a 1kg+ weight to come loose, and your GPU is directly below it...
I've used air-cooling and AIOs; I definitely prefer the AIOs but that's because I prefer silence (heavy air-coolers can operate as quietly as AIOs, but the weight issue turned me off). Custom water, which I'm venturing into now, is more complex but as long as everything fits it'll be fine...simple plumbing, and how often do the pipes in your house leak? Also, the idea is to leak-test a WC loop before you fire up a system...any component which suffers from a leak can be thoroughly dried before being powered up.
WC works by piping water through waterblocks, which go on your hot components. This water is then routed to a radiator that has fans providing a cooling airflow through them, venting the heat out of the case. Apart from allowing quiet operation and providing better cooling, WC allows you to set where the heat is taken out of your system, as opposed to having hot air circulating in your case.