More on what to spec: I don't know. People have been asking me a lot about specific shows, and I hate to go on the record with some official answer when it's a question that gets such varied answers. So this is as official as I'll get:
Spec a show that's in its 2nd season or later - but be wary of anything that's been on for 5 or more seasons.
Don't spec a show that looks like it might be cancelled soon. This can be hard to tell, but if you check in with the trades (Variety and the Hollwood Reporter) every now and then, you should have a sense of it.
Spec something that demonstrates your best qualities as a writer - whether it's witty banter or plot twists or broad comedy. It should be the kind of show you want to get staffed on.
Most importantly, spec a show you love and that you're passionate about. If you pick a show because you think it's popular or commercial or the Right Thing To Spec but you don't enjoy writing it, then that will show through in your writing.
Otherwise, it's up to you. Pushing Daisies? I say sure, go ahead. But I'm not the all-powerful beacon of TV spec knowledge. I guess I know more now that I used to, though, or I wouldn't have written a spec of The OC between seasons 3 and 4. :)