Computer Apps, without the nationwide aspect.
Kind of late for the passive e-commerce webpage, but maybe.
Liquor - boutique distillery, micro brew beer or wine.
In general, manufacturing something that has enough value and profit margin to allow it to be sent UPS should work. Notice, none of these things are the standard, Southern Illinois style, cheapest thing in the price category. Higher value items, with less numbers of sales and more profit per item hold more promise.
What kinds of businesses could be successful in Southern Illinois?