I feel The Simpsons should always retain the title of best cartoon series as it paved the way for all the cartoons we have now & the first several series were really brilliant.
The Venture Bros., however, comes a close second. I did not like it at first, mainly because I watched it a few episodes in &, like The Wire & The Sopranos, had not witnessed the storyline & character build. 4 series in, & I'm still hooked. As a continuation series, it doesn't leave big gaping holes in previous storylines or erase past events like most cartoons do. If a character dies, cuts their hair, ages, loses a limb, it stays that way. The storyline is brilliant & at around 10 minutes long, it's pretty easy to breeze through a whole series in a short amount of time.
I'd highly recommend to any Adult Swim, comic or cartoon fan to watch it/download it NOW.