An unflinching spoof that targets classic movie westerns of yore as well as life in the American West, circa 1882, "A Million Ways to Die in the West" is a spirited concoction that is one part "Blazing Saddles" and another part "Back to the Future Part III" as processed through the self-deprecating mind of Seth MacFarlane. For the multi-hyphenate MacFarlane, his second live-action directorial feature is more confident and focused than his first, 2012's bloated, narratively paper-thin "Ted," even if he still too often falls back on crass and/or pedestrian pratfalls and gags that betray his otherwise incisively funny satirical bent. The screenplay, co-penned by "Family Guy" writers Alec Sulkin and Wellesley Wild, is uneven, sometimes hitting subversively astute targets and other times lamely going for the obvious. The excellent cast, though, keep things cooking, giving into the ridiculousness of the material while bringing the same commitment that one would to a prestigious period drama.

Living in the dusty Arizona township of Old Stump, Albert Stark (Seth MacFarlane) is an honest, good-hearted sheep farmer who doesn't possess the gun-slinging, bar-fighting machismo which surrounds him. When beautiful girlfriend Louise (Amanda Seyfried) breaks up with him, claiming that she wants more out of life now that the life expectancy has passed the age of 35, he is devastated by the news. He desperately wants to get her back, even after she begins dating the wealthy, mustachioed Foy (Neil Patrick Harris), and feisty new-girl-in-town Anna (Charlize Theron) decides to help him out with this quest. As a planned pistol fight between Albert and Foy draws near and Anna begins to grow feelings for this sweet guy who is anything but a loser to her, it is only a matter of time before her seedy romantic past with jealous, cutthroat bandit Clinch (Liam Neeson) comes to light.

"A Million Ways to Die in the West" gets off to a discouraging beginning, Albert's introduction punctuated by him falling down as he runs through town. The viewer might recoil at the thought of the next two hours playing on no level higher than this, but then it gets better—sometimes much better. In his first starring film role that does not involve him voicing a foul-mouthed teddy bear, Seth MacFarlane is so sincere, so sympathetic and, dare it be said, so adorable that his Albert instantly becomes an unlikely hero worth rallying. A monologue he delivers as he tells virginal best friend Edward (Giovanni Ribisi) and Edward's God-fearing prostitute girlfriend Ruth (Sarah Silverman) all of the ways in which the time and place in which they reside is awful becomes a fantastically searing comment on the rotten, deadly way of life in the 1880s. Jokes about how easily barroom brawls can break out and the archaic photography from the era—"made by lightning and God himself!" reads a sign at the county fair—follow in quick-witted measure, mixed with a smart brand of racial humor that serves the same purpose as much of the material in Mel Brooks' "Blazing Saddles" without that picture's queasy undercurrent of behind-the-scenes bigotry.

Charlize Theron's (2012's "Snow White and the Huntsman") esteemed career trajectory has led her to a lot of serious—and seriously dark—projects, so it is all the more gratifying to see her let loose here as Anna. Although she harbors a secret that puts her and her growing relationship with Albert in jeopardy, there is a delicious lightness to Theron's performance that should not be mistaken for apathy. Quite the contrary, she dives into her character and her harsh circumstances while still retaining the drive to have fun and all the headstrong characteristics—intelligence, kindness, fortitude—that one hopes for in a friend or romantic partner. Anna and Albert—and Theron and MacFarlane—are the soul of the film, and the biggest reason for its success.

Their ensemble co-stars are almost entirely without fault, even when they aren't quite used as fully as they could have been. Amanda Seyfried (2013's "Lovelace") is a game presence as the materialistic Louise, best when she comes close to throwing down with Anna and exhibiting a fine sense of humor when her naturally wide eyes are worked into the script. As Louise's pompous new beau Foy, Neil Patrick Harris (2013's "The Smurfs 2") achieves something very difficult: he remains oddly irresistible even as he is clearly set up as a smarmy antagonist. By contrast, Liam Neeson (2014's "Non-Stop") is the true villain as the deadly Clinch, and has less chance to make more of his part than simply that of an immediate threat to Albert and Anna. Neeson fulfills what is asked of him, but he is also basically an annoying means to an end, there to provide conflict. Giovanni Ribisi (2013's "Gangster Squad") is certainly affable as Albert's best buddy Edward, but it is Sarah Silverman (2012's "Take This Waltz"), as Ruth, who steals all of their scenes. A Christian who won't have sex with Edward before they are married but thinks nothing of sleeping with fifteen paying customers per day, Ruth is blissfully clueless, the kind of woman for which the term, "hooker with a heart of gold," was created.

If the general premise of "A Million Ways to Die in the West" is on the plain side and it is never quite as uproarious as it should be—an extended hallucination sequence at the start of the third act could have been excised from the final version, cutting five precious minutes from the 116-minute running time—there is something to be said for a western where the protagonist gains a backbone while refusing to otherwise change for anyone. It is also the kind of joyously absurd film where 9-year-olds get married out of fear of becoming 15-year-old spinsters, so it's got that going for it, too. Even when "A Million Ways to Die in the West" takes a tumble, it never loses its winsomely sunny, eager-to-please disposition. This—and the pleasure of watching the movie's charismatic actors mix it up—makes it all worthwhile.