I've decided that the next amp I'm going to buy is a Mesa Express 5:50...

However, I don't know which version I want to buy...1x12 or 2x12. I know that there are differences in tone between the two configurations, but here are my questions...

What are the differences?

What if I get a 1x12 combo and a separate 1x12(or more, but probably not)cabinet? How does this effect tone?

More speakers -> more air being moved -> MOAR LOUD!!!
Even if you compare two amps of the same wattage, the one with more (or bigger) speakers is the louder one. Also, several (or bigger) speakers are better at pumping out the lower frequencies, which is very helpful for a fat rock and metal sound.
This is not only due to the speakers though, it is influenced by the cabinet the speakers are set into. The larger the cabinet, the better the bass response. Naturally, cabs with several speakers are bigger (most at least). That's why a 2x12 cabinet has a better bass response than 2 1x12 cabinets.
If you want a fatter sound, the 2x12 is the better option for you. If you don't care though or if you prefer a lighter sound, the 1x12 will suffice. The difference in volume doesn't matter much because the combo is plenty loud with both speaker configurations.