There are obviously many ways to look at how the last episode ended. My personal view is that we are brought full circle to the beginning. Lois's line "Don't tell me you can't do it" reminded me of the beginning when she was telling Malcolm he had to do the Krelboyne class because he was able to.
Also, I believe that the president reference is meant to forshadow that he does become president. Malcolm's last shot being him as a janitor shows two things. First of all, that Lois was right about the path he would take. Second, the irony of both him and Reese being janitors even though Malcolm has gone through much more to get higher.
As for the Lois' Skeptics, I was always of the belief that she was looking out for her sons. She definetely is one of the main reasons for the dysfunctional relationships within the family, but she also keeps it together. There are many examples of when she is looking out for her sons and is not aiming to punish them. One example is the Long Drive where she knows Malcolm is going behind her back to visit his girlfriend, but she ignores it. Another is one of the clip shows when at the end Dewey is hurt and she and Hal handle it perfectly- except they have the wrong juice- making them believe they are bad parents. I feel that clip explains that the boys are really Loi's main priority, she is just "crazy." Just as at the end, she kind of goes of the handle telling Malcolm is GOING to become president. She cares, maybe too much, which is why she is viewed as an antagonist.
Sorry, Damn. Stupid. I can't do it. I'm stupid and I'm terrible. I suck at everything... and I'm fat.