We've been seeing a lot of clients Switch to Bolt's checkout. This includes sites like ShopAkira.com. If you click checkout in the cart, you get Bolt's highly-optimized checkout, which, by the numbers, shoppers like a lot more than native Magento. I've seen it generate significant conversion increases.
For users that want or need to keep everything on Magento, and not a hosted solution like Bolt, I'd definitely look at OneStepCheckout.com, or an extension from Amasty or AheadWorks. I know that everyone has their favorites, which can be dependent on the extensions that they're already using that need to interact with the checkout.
While I'm sure that some exist, I can't think of a Magento site that I've seen do a great job of customizing the checkout without an extension or integration.
Best of luck!