I have an RME UCX which is just big enough for a 4.1 system with headphones. It has one analogue output spare -> 4 + 1 + 2 = 7. If you think you might need more than that in the near future then you might want to opt for its bigger brother.
As for speakers, if finances permit, I would just pick one of the "well thought of" active monitor speakers from Adam or Genelec. I bought some Neumann KH 120A's which is another option. If you think you might end up with a dozen speakers with a C/C# split, for instance, then you might want to consider the final cost as well as the initial cost.
A possible problem with active or powered speakers is that they need both an audio connection and a mains connection. Even for quite small cable runs that can be inconvenient.
As for sub-woofers I like the ones from BK Electronics. They are not available in hi-fi shops probably because they are OEMs for people like MJ Acoustics.
http://www.bkelec.com/ One of their XXLS400's fills my small room without any problem. I seem to recall that someone here used a couple of their Monoliths to fill a church.
(I have no connection with any of the companies mentioned above.)
EDIT: It might be worth mentioning that my set up is quite compact and the advice above relates to that. I have the speakers (nearfield monitors) only a few feet away and pointing straight at me - like big earphones
If your requirements differ then that may affect your speaker choice.
Regards,