I've often pondered this question. I've been reading a lot of the answers and many of them point to drugs that are not even widely abused. Avoid heroin, crack, and meth. I would not try any of those drugs even once.
For that matter, I consider the whole class of opiates or opiate-like drugs to be a very bad idea for use on a regular basis. These drugs are very addictive and very pernicious. The worst part is heroin addicts never recover full functionality. Even if they get totally clean, they're often beset with long lasting problems such as depression and low libido. Heroin addicts give true meaning to the term "junkie."
In the world of drugs, there is a clear dichotomy between uppers and downers -- that is, between stimulants and depressants. Physical addiction is the epitome of addiction, writ large. This is a veritable problem that manifests with just about any downer including alcohol, barbiturates, benzodiazepines and opiates. That reminds me; I would never try barbiturates.
I'm a big fan of stimulants, so why would I never try meth or crack?
I believe there is no safe way to use meth. "Normal use" easily escalates and becomes disruptive to one's structure and routine. Strictly speaking, one recreational dose of meth will have a person amped up for 12+ hours. Allot eight hours for sleep. That leaves four hours or less for eating and working... It's manifestly unsustainable. Meth has been linked to Parkinson's; it's known to be neurotoxic. Also, meth addicts (habitual users) who get clean struggle with intense psychological effects (namely cravings to use again) which linger long after cessation of use. Meth addicts are known to self-destruct and engage in activities (esp. while abusing for several days, aka "tweaking") that are highly dangerous to one's safety and well-being.
In general, cocaine use can cause sudden death, especially in high doses and for those with preexisting cardiac abnormalities. Although powder cocaine is cardiotoxic, crack cocaine is more habituating and damaging to the lungs and heart. It's prone to abuse, and when it's abused, it has damaging health effects on various organs.
As stimulants go, meth and crack almost invariably lead to the abuse of downers. The concomitant use of uppers and downers leads to a more recalcitrant form of physical addiction.