There are many reasons to oppose Rick Perry as President. His grades, however, are not one of them.
First, account for grade inflation (here is a chart of the average grade from 1940-2009: http://gradeinflation.com/figure2.gif). In 1968, the average gpa at a Public university was 2.7 (and some were tougher than that). Moreover, while the average grade has gone up over time, universities have grown less selective. A 2.22 in 1968 might be 2.8 today.
Second, academic success is a rather poor predictor of how successful a president will be (especially when you have far better indicators, like say, an 11 years of governing a large state). The biggest part of a President's job is salesmanship. If they are unable to sell an idea to the public, it will have difficulty getting through congress, and their agenda will flounder. The second-biggest part of the job is delegation. The President picks experienced advisors, who consult with very smart analysts on major questions. Its not like Obama is sitting in his office trying do run regressions on how to raise GDP right now. If the president doesn't manage his team effectively, the system falls apart. Probably the third-biggest part is making decisions. Here intelligence can be important, but isn't most of the time. Usually policies have tradeoffs - eg. cutting the corporate tax might increase inequality, but raise economic growth. Deciding whether equality or growth is more important isn't a right or wrong question - it is one of values.
Don't believe me? Well, perhaps consider that the top pick on Gallup's last "best president" poll was a mediocre student at a lousy school (Eureka College), whose professional life was mostly spent as an actor in B-movies.