Should I use two 2:1 mux or one 4:2 mux?
Functionally, the 4:1 mux could be seen as superior in that it allows you to later add a 4th input if you so desire; meanwhile, you can simply connect C to both the 3rd and 4th inputs as Eugene suggested to obtain a functionally identical circuit to a pair of 2:1s. 

If the 2:1 muxes (muxs?) are individual ICs, then the 4:1 is also superior in terms of design simplicity; you only need to worry about powering one chip instead of two, and the layout is a simple 4-in, 1-out, rather than having to wire/route the output of the first 2:1 into the input of the second.

There could still be reasons why two 2:1s would be preferable to one 4:1, but I can't think of any off the top of my head other than if the cost were lower or another party had specifically requested 2:1s. If you want to use 2:1s out of personal preference, though, you can by all means - they'll do the job perfectly well.