Well, this depends on if we're talking about the band(s) with the greatest mass appeal/sales, musical influence or just personal favorites. Metallica, Skynard, The Eagles, Van Halen and Aerosmith are probably the "biggest" American bands ever to record (with honorable mention to Hendrix, Garth Brooks, The Boss, Wakco Jacko and Billy Joel-though they are all artists and not technically bands). As far as influence goes you can't really top any of the old delta bluesmen like Leadbelly, Robert Johnson, Muddy Waters, Howlin' Wolf etc. They were the primary influences for the Beatles, Zep, Clapton and pretty much any band that has a guitar solo. Almost all of rock music can be traced back to these roots. Personally I tip my hat to Bad Religion, Rancid, Nirvana, Pearl Jam and the the Ramones as favs. If I had to pick one band though, I'd go with the Grateful Dead. Yeah, it's not for everyone and some it does kinda suck out loud, but factoring in longevity, generation bridging and faithfulness of the fans they're my pick. The sheer amount of music they played and recorded and their main-streaming of the festival scene has to count for something. Plus, Jerry was the meanest 3 fingered guitarist ever!