Indie films are usually more artistic, though that fact is often overshadowed by their smaller budgets and lack of upscale production facilities. A fine example would be "The Legend of 1900," which was an independent film that won various awards for its stellar storytelling and creative effects. It was not produced by Universal, MGM, or the other mainstay studios of Hollywood, but rather, by a small operation run by a few select people.
Hollywood or mainstream pictures usually have all the technological effects and glitzy "tricks of the trade" to draw in viewers, while indies are largely responsible for their own success through the basics of quality filmmaking. In addition, mainstream flicks also include enormous advertising budgets, while indies are normally limited in their promotional efforts.
The major difference is usually whether it was produced by a large well budgeted Hollywood ("mainstream") production house for the sole purpose of generating revenue, or if it was produced with a more artistic purpose in mind. Generally a lower budget, a risqué or taboo topic, and a limited release to smaller audiences at a time is considered to constitute an Indie or an individually produced film.