MXE wasn't designed at random; it was the chosen winner of a long series of tested compounds made by a chemist who had no other way to treat his phantom limb pain. We have a huge thread at bluelight of people's ideas for chemicals that might get you high, but the first thing you'll notice is that basically all of those ideas are infeasible:
http://www.bluelight.org/vb/threads/582708-I-like-to-draw-pi...
The degree of effort to which people will go to satisfy their curiosity is sort of astounding. There seems to be an endless array of possibilities. The thing is, people who have some understanding are always trying to direct attention to structures that won't cause grievous physical harm, stuff we understand, and so it is usually these that get popular -- there's a reason that synthetic cannabinoids have fluoropentyl chains on the indole nitrogen instead of fluorobutyl chains, and it's because the latter will tear your mitochondria to shreds (fluoroacetate). Unfortunately, as more stuff gets banned, we stray further and further from the beaten path -- methylone was pretty similar to MDMA, but we know a lot less about 6-APB, and whatever comes next will probably be even stranger. Every now and then the predictions fail and something nasty like 5-API shows up on the market and people die, and we don't know what to do about that because there will always be effects we can't predict. Even as we do our best to recommend the things we think are safer, we inevitably shuttle those off the pipeline into prohibition and rush forth to the next scary-looking arylalkylamine.
It's a mess. Most people in the harm reduction community want legalization, but none of us wants this. We actually have plenty of drugs that have a history of use and no reported deaths (mephedrone, 2C-B), but of course those got banned, anything that becomes popular gets banned, even if it appears to be safe (Al-LAD on the chopping block) and we go back into the dark again, waiting for the tide of profiteering to carve a new vista out of the world's insatiable demand for something more entertaining than football.