Ex-gambler John Alighieri (Steve Buscemi) tempts fate by returning to his hometown with a fraud debunker (Romany Malco) investigating a questionable car accident in St. John of Las Vegas. (KinoSmith)

With his spindly frame and worried-carp mug, Steve Buscemi was born to play losers. Specializing in greasy deadbeats (Reservoir Dogs), cranky misfits (Ghost World) and soulful sad sacks (Trees Lounge), he has a knack for making the most undesirable characters seem human, even likable.

The lively cast struggles valiantly to make the film work, but they are defeated at every turn by Hue Rhodes's poor directorial instincts.

Writer-director Hue Rhodes was clearly banking on the actor's considerable appeal when he created Saint John of Las Vegas. This sloppy debut initially seems tailor-made for Buscemi's gifts, but it proceeds to squander them in scene after pointless scene.

The movie begins with a keyed-up John Alighieri (Buscemi), twitching as he buys lottery tickets at a convenience store. John is a compulsive gambler who's left Las Vegas in the hope of leading a straighter life in Albuquerque, N.M. With the exception of the occasional binge on "Who's Your Daddy?" scratch n' win cards, John leads an unremarkable existence, working under the soul-sucking fluorescent lights of an auto-insurance firm. His only respite comes from stealing glances at a plucky girl named Jill (Sarah Silverman, deserving of a better role), who spends her days giving herself happy-face manicures in the cubicle next to John's.

Inspired by his crush, John musters up the energy to ask his boss for a raise. Mr. Townsend (Peter Dinklage, wasted in a tiny role) agrees but only if John accompanies fraud investigator Virgil (Romany Malco, always amusing) to Las Vegas, where the two men need to prove that an accident claim filed by a stripper is fraudulent. With that, Saint John of Las Vegas devolves into a hackneyed road movie, chock full of Sundance Lab clichés.

While driving toward Vegas, John and Virgil bicker incessantly. They're intended to be a modern-day Odd Couple, but despite the actors' best efforts to invest the dialogue with deadpan humour, exchanges like "Give me the keys so I can go back to the motel!" and "Screw you!" cast a miserable, sour pall over the proceedings.

The unlikely duo encounters a string of oddballs: two heavies at a desolate garage; a stripper performing a pitiful lap dance in a neck brace; a band of gun-toting nudists; and a carnival performer (John Cho) whose costume keeps bursting into spontaneous flames. Culled from the quirky school of screenwriting, these are types rather than characters, and they're given so little screen time that they barely register — save for Cho, who deserves kudos for providing the film's one genuine laugh.

Alighieri (Steve Buscemi, right) interviews a carnival performer (John Cho) in St. John of Las Vegas. (KinoSmith)

The cast members are lively and struggle valiantly to make Saint John of Las Vegas work, but they are defeated at every turn by Rhodes's poor directorial instincts. The movie's tone careens wildly from straight-up drama to wobbly comedy to the occasional abortive stab at something more surreal, and things are edited in a manner that feels wholly arbitrary — phone calls from Jill, time shifts and dream sequences pop up at random.

The result is a confusing mish-mash, and it might take a while for viewers to realize that Rhodes's references to Zippo lighters, Virgil, fire and a character named Lou Cypher are an attempt to make Saint John of Las Vegas a modern-day take on Dante's Inferno.

Through it all, Buscemi is a consummate professional, believable as a little guy having a string of particularly bad luck. He's good enough that you'll be willing to follow him on his journey through the circles of hell, but even he can't save this movie. By the time he reaches the movie's ninth gate, he's more haggard and drawn than usual, turning his bugged-out eyes to the camera in desperation. His imploring gaze is pure Dante. It says: "Abandon all hope, ye who enter here."

St. John of Las Vegas opens in Toronto, Montreal and Vancouver on Feb. 5.

Lee Ferguson writes about the arts for CBC News.