I believe it could work, because in the three games I viewed closely, against the Dolphins, Saints and Steelers, the opposing offensive coordinators did not make working Mario Williams into coverage a priority in the passing game. And how often have you seen or heard of an offensive coordinator designing his passing game plan around a running back? Mike Martz did it with Marshall Faulk, but nobody tried covering Faulk with a power outside backer. You might have some key plays for a back, if you're a Sean Payton and you've got a Darren Sproles in your arsenal, but you don't enter a game counting on matching up a back on a linebacker 8-10 times and getting 120 yards of offense that way.
Houston's opponents wanted to attack down the field and used a lot of spread sets. This gave Houston an advantage against four and five man patterns, because tight ends were rarely on the field and because the backs these teams used had to stay in much of the time to help block. This meant more four-man routes and less pressure on the Texans back sixes and sevens.
When Phillips knew spread sets were coming, he put Williams in his familiar 4-3 role on the left side. He's long-armed and abused the right tackles he faced. When he got one on the down-slide, like Miami's Marc Colombo, Williams regularly got into the quarterback's face.
Having seen Williams in a 3-4, I believe Rob Ryan could make it work. He's got fast inside linebackers who can cover. He has a strong safety who can cover pretty well when he's healthy. In his pipe dreams, I'm sure Ryan would like a Williams and a good, penetrating DE, giving him a good rusher everywhere across his front five.
Williams' contract demands will likely keep this in the pipe dream category, but what a dream.