I've struggled with this too.
I am going to go with Boston Pro 6 inch separates in the front and rear. I've noticed that the speaker manufacturers offer their high end speakers in the round versions, and items like 6x9 and 4x6 are only available in their middle and low end lines.
Bottom line though, is its really dependant on what level of system you are looking at.
For a simple upgrade, with little or no additional amplification, the 6x9 should be fine. But for a more involved system, with a sizable amp, I'd stick with round speakers. I'm going to run an A/D/S PQ20, so driving the speakers will not be a problem.
Of course, in any case, pay attention to the specific speakers' power requirements.
One advantage of the 6x9s is that they typically offer more bass than the 6.5 - useful if you aren't running any subs.