"Looney Tunes Back in Action"'s extreme failure at box office is the reason why you hardly see Bugs Bunny and Daffy Duck and company anywhere these days.

It was also the reason why Warner Bros. Feature Animation shut down (but then again, all but one of their films, the inferior "Space Jam", flopped anyways.)
"Brother Bear" also bombed, if I recall correctly. In fact, nearly every animated movie released in 2003 that wasn't "Finding Nemo" flopped.
But "Home On The Range" didn't necessarily bomb because it was 2D animation, it bombed cause of its weak story! Farm animals had been done to death by that point
"Snoopy Come Home" also bombed when it was released in 1972; it only had a million dollar budget but returned roughly $200,000 or so. I don't think any of the other Peanuts features after that ("Race For Your Life, Charlie Brown" and "Bon Voyage, Charlie Brown") did very well at box office either.
If I recall, "Bolt" didn't do so well last year either.