By Emily Exton
Updated May 13, 2010 at 06:44 PM EDT

Image Credit: Glenn Harris/PR Photos“God Karen you’re so stupid!” high school tyrant Regina George exclaimed to her daft minion when she stupidly suggested that they go to Taco Bell. (She was just trying to cheer her up!) Sure, Karen wasn’t the brightest crayon in the box — she was confused by genealogy and thought that ESPN was a fifth sense — but Amanda Seyfried, who portrayed her in the film, may be the smartest of all her Plastics counterparts. Or just the luckiest.

Six years after the release of Mean Girls, the film stands as a cult favorite. It’s a quotable landmine and a genuinely accurate depiction of the wild animal kingdom that is the high school girl-world. While its themes and funny one-liners remain timeless, the players who brought them to life, and their careers, couldn’t look more different now. In 2004, Lindsay Lohan was poised for Hollywood domination. The not-even 18-year-old was already a bankable Disney star, and was eying edgier, more mature roles (thanks to those pubescent changes). Next to her three co-stars, she was the one we thought was poised for super-stardom.

But things change. Today, Lohan remains engraved in our pop culture consciousness, thanks to endless tabloid fodder, but as an actress, her resume looks a little thin. (Anyone want to admit to seeing I Know Who Killed Me?…anyone? Bueller?) Party of Five‘s Lacey Chabert, the second “biggest name” on the Mean Girls bill at the time, has done mostly voice work since the film, with the exception of a role in Matthew McConaughey’s forgettable Ghosts of Girlfriends Past. Of course, Rachel McAdams has hardly disappeared (thanks in part to TBS and ABC Family for their constant looping of The Wedding Crashers and The Notebook), and is perceived as an actress with longevity, but in 2010, Amanda Seyfried is arguably the biggest success story to come out of the Tina Fey-scripted film. Her third film this year, Letters to Juliet, hits theaters tomorrow, positioning her to become a romantic film staple. And since Mean Girls, she’s shown she can handle sappy tear-jerkers (Dear John), darker indies (Chloe), and campy high-profile musicals (Mamma Mia!), all while pulling her own weight alongside more seasoned actors (Meryl Streep, Julianne Moore, and Colin Firth).

For Seyfried, the journey was slow but steady. She did a few guest spots on popular television shows (Law & Order, House, Veronica Mars, CSI), followed by a series of smart, yet risky, choices: Big Love and Mamma Mia! ultimately paid off. Mamma Mia was the fifth biggest film of 2008, and Big Love has raked in critical acclaim over the course of its four seasons (season five premieres next year). On deck for Seyfried: Albert Nobbs, with Glenn Close, Jonathan Rhys Meyers, and Orlando Bloom, and The Girl with the Red Riding Hood with Gary Oldman and Julie Christie. Not bad for the girl whose breasts can tell when it’s already raining.

But could you tell Seyfried would be a contender for Hollywood Queen Bee simply from her vastly underrated performance in Mean Girls? Her role consisted of mostly blank stares and a few aptly timed silly comments, but maybe that was the brilliance of it. In a way, Karen Smith is to Mean Girls what cheerleader Brittany is to Glee: A blonde scene-stealer with an incredible knack for deadpan.

Did anyone expect Seyfried’s career to explode and Lohan’s to self-destruct? Should we chalk it up to talent, project choices, personalities, or merely luck? Should Lohan do a Nicholas Sparks film to get back on track. (It certainly couldn’t hurt.) And do you, like me, find yourself randomly quoting Mean Girls throughout the day? Oh my God, Danny DeVito I love your work!