Hollywood’s vast warehouse of rom-coms is so overstuffed it seems almost hubristic for anyone to attempt a fresh approach and expect to engage audiences who have seen it all before. “What If” just manages this daring feat, largely on the strength of Zoe Kazan’s enormous appeal, with an able assist by Daniel Radcliffe, who here makes another smart post-“Harry Potter” career choice as her lovelorn pal.

Wallace, a Toronto med-school dropout and dispirited serial suitor, is decidedly down on love, calling it “an all-purpose excuse for selfish behavior.” But when he and animator Chantry (Kazan) meet cute over magnet poetry at a party, he squelches his instant attraction to her when she mentions that she’s been living with a lawyer for five years, so that they can at least be friends.

Kazan has honed the quirky-girl persona she trotted out in “Ruby Sparks” to understated perfection. The new buddies cement their simpatico sensibilities by discussing poop — specifically, how much of it Elvis and other celebrities had left in them when they died — over a late-night diner nosh.

Although the pace occasionally slows, notably during a touching, gorgeously shot skinny-dipping/stargazing scene, the rest of the movie is mostly a series of talky vignettes spiked with the occasional prank or pratfall, rolled out rat-a-tat as if targeting short attention spans. The tactic at times annoys but generally staves off the restlessness induced by dialogue overkill. Comic relief is further provided by the frequent strategic use of sidekicks Allan (Adam Driver of HBO’s “Girls,” who manages to be adorable even while chewing his fingernails at a jewelry store) and his brash girlfriend Nicole (Mackenzie Davis, a Canadian we’re sure to be seeing more of).

The story falters and drags a bit at the end, perhaps inevitably as there’s really no new denouement territory left to explore in this genre. But by this time, we’re rooting for these two crazy star-crossed kids to get together already.

“What If” mashes up themes previously explored in the iconic boomer film “When Harry Met Sally” and Gen X’s movie-as-mantra “Reality Bites,” then distills them through a modern twenty-something’s worldly lens. This sweet little movie peppered with crude age-appropriate humor is a palate cleanser to savor between the cartoon blockbusters of summer and the serious cinema of fall.