I run a heavily modded version of oscommerce, but you need to be slightly techy to run it.
I've looked at Lightspeed
(Mac based) and it's pretty fantastic. I know several small businesses that use and love it.
If you want to run a CRM, you aren't going to be able to do it on a cash register, unless you spend ALOT of $$ getting something integrated.
You wouldn't need a cash register, just a cash drawer.
I just can't justify the $$ to change over, when I have invested so much in oscommerce to get it the way I want it.