Well, let's just make a list of potential candidates:
Lynyrd Skynyrd
The Eagles
Jimi Hendrix (my vote, btw)
Metallica
Aerosmith
Poison
Guns N Roses
Boston
Pearl Jam
Nirvana
Van Halen
ELVIS PRESLEY (seriously, can't get much greater than that)
There is, of course, a lot more. This was just from a cursory scroll through my iTunes library.
...does Rush count? They're Canadian, which you could say is 'american'.
What were you saying about no serious contender to Lynyrd Skynyrd?
EDIT: right, the post above me reminded me of some more: Bob Dylan, The Beach Boys, Tom Petty.
To stray away from the rock stuff, though: Michael Jackson, The Temptations, Robert Johnson, Son House, The Supremes, Smokey Robinson and the Miracles, Stevie Ray Vaughan, and much much more.