The long-haired performer chopped off his somewhat stereotyping locks and soon landed series work, taking regular supporting roles as likable one-note characters on the low-rated working-class themed sitcoms "Love and Marriage" (Fox, 1996) and "DiResta" (UPN, 1998-1999). Between these roles, he appeared in a two-episode guest turn in the 1996-1997 season of "Murphy Brown", playing Danny, the delinquent son of Dana (Julie Hagerty), the new love of Frank Fontana (Joe Regalbuto). Danny and Murphy (Candace Bergen) get into some trouble on an Atlantic City gambling spree in a memorable episode penned after Palladino's successful first appearance on the show. While the numbers showed that few viewers saw the actor's regular TV work, he honed his skills on the small screen and was prepared when he landed a more challenging role in the 1999-2000 season of the popular NBC drama "ER". Palladino played Dr. David Malucci, a cocky second-year resident whose confidence and passion for medicine spawns an irreverent attitude toward hospital procedure. "ER" would offer the actor breakthrough opportunities, meeting with his largest viewership to date in a compelling supporting regular role with room for growth.

Palladino made his feature debut in the 1998 teen comedy "Can't Hardly Wait" as a young man with creepily amorous intentions toward his newly-single golden girl cousin (Jennifer Love Hewitt). Following this cameo, he racked up credits and proved his talents with larger roles in small-scale independents. Among these efforts was his starring turn in 1998's "The Week That Girl Died", where he played one of a trio of friends who each unexpectedly meet women and embark on quickly consummated relationships. As Vinnie, the man who meets his partner at a funeral home only to find the devious woman harbors some dangerous secrets, Palladino affably played a flawed dupe. He followed up with a well-acted, scene-stealing turn in the 1999 feature "This Space Between Us", portraying the plain-speaking pal of the fledgling director protagonist (Jeremy Sisto). That same year, Palladino starred opposite Jennifer Rubin in the festival screened "Road Kill", playing a film student who accompanies his hit woman neighbor on a road trip, documenting her final crime spree in an effort to turn in a groundbreaking final film school project. Here he managed to flesh out and bring audience interest and sympathy to a character that could ostensibly have come off as a one-dimensional movie geek. Following his newfound "ER" notability, Palladino was featured in the star-studded cast of "U-571" (2000), a World War II drama directed by Jonathan Mostow set on a submarine. The film interestingly co-starred rocker-turned-actor Jon Bon Jovi, whose videos the former VJ used to enthusiastically present.