Do speaker cables really make a difference ?

After getting my Pioneer SX-1280 back from a full recap, I wanted to upgrade the old "by the roll" 16 gauge wire with 12 gauge.  I had already upgraded the crossovers on my HPM-100 200w version speakers which included banana plug posts.  So with the addition of 12 gauge push terminal to banana plug adapters on the SX-1280, I purchased Mediabridge 12AWG Ultra Series 12 FT cables.  For what I need It is solid.  (And the cables are reasonably priced). 
 

Bottomline, make sure what you have is solid as It relates to gauge, material, connectors and you will be fine. 

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They most certainly do make a difference. I recently moved things around and had to sell my Morrow Audio SP-6'S because they weren't long enough for my current configuration and replaced them with a pair of second hand Canare 4S11 cables and hooked them up bare wire and let me tell you that everything collapsed and sounds thin as all hell with no details! I'm glad that I only paid $40 for the Canare cables. What a disappointment! If anyone has used the Morrows close to the SP-6'S and knows of something close to that sound quality please let me know. I'm disabled now and can no longer afford to buy the Morrows brand new. Any help is appreciated.

Yes - 100% the do make a difference but they are system dependent as well as dependent on how you hear and perceive things. What works for me in my system may not be the best for you. 

If just trying things out for the first time, try out a few different brands that fir your budget. Ideally, listen in your system and then buy the one you like best. 

The better your equipment, the more difference they make.

I can hear a difference between some QED silver cable from 20years ago and Wireworld eclipse 6s that I have much more detail in the wireworld