Date Rape by Sublime. May not be their biggest hit, but it was their first, and it is a truly awful, terrible song that I feel set their careers and their legacy way back. They are a much better band than this song indicates.
“Short People” isn’t a total departure from Randy Newman’s usual style, but a lot of people who sang along to it on the radio would have been shocked to hear “God’s Song” or “Rednecks”.
“Jump” doesn’t have what’s arguably the most distinctive thing about Van Halen - Eddie Van Halen playing the guitar.
You might want to check back on that…Eddie plays a pretty good solo in that song. But you are right that everywhere else in the song is guitarless (unless maybe there’s some guitar-synth).
I’m not sure if it’s their biggest hit or not, but I think it’s sad that there are a lot of people who only know Dire Straits as the “Money For Nothing” guys.
Yeah, it’s funny that Dire Straits only became superstars after releasing a song that sounded exactly like ZZ Top. 
Like A Rolling Stone certainly was indicitave of Dylan’s style but hardly the best representation of his talent. Yet, I believe that one was his biggest single (in the U.S. anyway)
And even funnier that the whole song parodies music industry’s sellout to the MTV mindset and here they go playing a song that sounds fairly generic and lo and behold. It becomes the song that put them on the “Pop” map.
Genesis-Invisible Touch.
Amen brother! I still can’t wrap my mind around how then went from post Peter Gabriel “Duke” and “The Wind And The Wuthering” to “Invisible Touch” The mind boggles.
For Your Love by The Yardbirds fits in here somewhere, I think.
“Hey Joe” wasn’t a Hendrix original, though.
I’d go with “Town By Malice” by The Jam or “Our House” by Madness, which were their biggest hits in America (both groups were more well-known in the UK) but weren’t really indicative of their sounds.
You are correct! It’s been a while since I listen to the original (as opposed to, say, Paul Anka’s version).
The Beach Boys - Kokomo (yuk!)
Actually, “Without You” was his biggest hit but even that was atypical of his work since Nilsson wrote most of his songs and “Without You” was a cover (as was Nilsson’s second biggest record, “Everybody’s Talking”).
The same thing can be said about Warren Zevon’s “Werewolves of London” which was a throwaway novelty song that ended up becoming his biggest hit and the song most people knew him by (much to his chagrin).
Also, I hate to say this but I think it’s highly likely “Stacy’s Mom” will end up being Fountains of Wayne’s biggest single and the only song most people will think of when the group is mentioned.
Tull’s biggest (and only Top 40) hits were “Living in the Past” (#11) and “Bungle in the Jungle” (#12). Although it is one of Tull’s best-known songs, “Aqualung” was never released as a single, so it was never a hit per se.
Apparently Blue Monday was New Order’s biggest hit. This drives me nuts, because I hate that song.
This happens a lot - whenever an act touches a mainstream nerve or tries something different for just a song, they get a hit.
Pearl Jam - Last Kiss
311 - Amber
Ben Folds Five - Brick
Green Day - Good Riddance (Time of Your Life)
Fountains of Wayne - Stacy’s mom
Hey Joe is not a Hendrix original.
Actually, Todd Rundgren’s biggest hit was “Hello It’s Me” (#5 pop in 1973), which is much closer to his usual style. Frank Zappa is one that popped to mind:“Valley Girl” (#32 pop in 1982) doesn’t have much to do with his usually more complex work. Then again, considering how incredibly diverse his music was, I’m not sure what would be a typical Zappa song.
Somewhat related is the issue of bands whose biggest chart hit wasn’t their best known work. I don’t think anyone instantly associates AC/DC with “Moneytalks” or Rush with “New World Man”, but they outcharted their far better known songs.