Well?
So many to pick from... Anybody been in the game for a minute?

Provide us what you need, so that we are able to offer some suggestions. The term "best" can be different for different requirements.

Take a look at Magento Commerce. It is one of the best open source shopping cart in the market.

It really depends on the scale of your operation and budget. If you're running a multi-million dollar ecommerce enterprise the answer is very different than if you're running a medium/small startup and different again if you are starting a part time business.
For example; BlueFly.com spent many millions on a custom ecommerce an ATG ecommerce platform.
We've worked with some smaller clients that do really well on ASP.NET Storefront and some even smaller ones that do well on the BVSoftware.com cart.
If I were considering a startup ecommerce business and I had I reasonable budget I'd lean more towards a commercial cart like ASP.Net Storefront than I would the low cost or free PHP carts. None of low end carts them really seem to have the features esp on the SEO side that some of the $1000 to $5000 commercial carts have.
If you're looking for a part time business, low vol business, a business that doesn't need great SEO the free/cheap PHP might be your best bet.
As far as SEO I've seen few carts that do it better than ASP.NET Storefront and BVSoftware.com to me the SEO features alone make those carts worth the money.

Well?
So many to pick from... Anybody been in the game for a minute?
First give more information, what You need and what You want to sell.
I am fan of Open Source shopping carts - and until now - the simplest, easiest and best looking software is PrestaShop for me. But there are about ten big open source competitors also - all have pros and cons.
I have tested many these carts and set up demos also - to know what features it has, what possibilities etc.
But my demo site is not yet 100% ready - I have only ZenCart, WordPress e-commerce solution, PrestaShop 1.0 and PrestaShop 1.1 dev demos up and running.

I think Ubercart has the potential to stand as an overall most reliable shopping cart.It is marvelous.But yet there is a business model out there the service for free to clients.Ubercart is built in php by those guys at Drupal.org.It has many settings to configure but when you get tt right,it is simply just amazing.It gives you the freedom to market your products in a professional platform including managing your affiliates.There is just much to talk about this ecommerce tool

I am fan of Open Source shopping carts - and until now - the simplest, easiest and best looking software is PrestaShop for me.
Until now? Does that mean you've changed your mind?
BTW, I tried looking for U.S. based examples of live sites built with Presta but couldn't find any. Do you know of any?

We dig good ole osCommerce for the entire shi-bang. Although, sometimes I wish we went with one of it's hybrid cousins. The initial feature set with like OSCmax is a bit more painless, as the "cousins" have many of the best modules already implemented in the install feature set.
NOTE: you do have to be a bit technically saavy with PHP if you really want to get the best bang out of it. It's not too bad if you understand "IF THEN ELSE" :P
Paul

My vote goes to Virtuemart for Joomla!. It has a huge comunity and ties in with payment processors very easily.

When considering a cart, I'd consider the environment it runs on at the same time. Magento is excellent but can run like a dog on a shared server for example if you are getting plenty of action.

As everybody has already pointed out, it all really depends on your budget. In my humble experience, I would narrow it down to two general cases:
1) (Almost) No budget, starting off project, no high traffic: Open source e-commerce solutions are your best shot. I've tested Magento, OsCommerce and Zencart. I would strongly suggest the latter for its enhanced features based on OsCommerce, its large community that adds new modules every now and again, and the long time they've been established. Magento works rather on the visual aspect, but it might get very slow when dealing with lots of traffic (as far as I've experienced).
2) Medium-high budget, high needs in terms of traffic and security: I have scarce experience in this field, so I would rely on my experience as a programmer: if you've got high needs and some money to invest, pay for your soft. In case something goes wrong, make sure there's someone in the phone to help you out. ;)
There might be specifics, of course, but generally speaking... that's how it has worked for me.
Cheers,
Solinger.