HFCS is more of a "super sugar" than a sugar substitute. Fructose is a natural sugar, and HFCS in its pure laboratory form is only a highly concentrated fructose derived from corn. (high fructose corn syrup).
For me at least, it is a health concern since if I eat or drink some things that contain HFCS I am more prone to asthma attacks. This may not be due to the HFCS itself; it may be some impurity in food quality HFCS, or it may be some other additive that is commonly used with HFCS. I don't care: I know if I avoid HFCS I don't have asthma; otherwise I often have exercise induced asthma which really limits my bicycling.
HFCS is used in foods and drinks for a couple of reasons: it has a sweeter taste than sucrose; it has a documented affect on depressing satiation so people consume more of the product than if sucrose was used; and I think because it is a liquid that is often shipped in railway tanker cars its delivery costs to the food factory are cheaper.
Fructose is a form of sugar that has to be converted in the liver to a different form before it can be used. HFCS puts a strain on the liver, and the blood glucose regulatory mechanisms, that does not occur with any natural foods. Anyone with a history of hepatitis, hypoglycemia, or diabetes maybe would want to avoid HFCS.