Coinbase.com is by far the easiest in my opinion (and is a YC company). Unlike MtGox.com (originally the most popular) the site is fast, stable, well designed, and can connect directly with your US bank account. They've also got a set of merchant tools and APIs.
Since we're throwing out referral links here apparently, this link will give you and I both $5 in BTC:
I'll second Coinbase as the hands down best choice for US merchants looking to sell (you get your first million in sales transaction fee free) and US citizens looking to buy coins (dead simple instant identity verification and linked directly to your bank account no shady third party money transmitters or wire transfers required).
There is one caveat. Coinbase isn't a real exchange in the sense that you can't buy and sell in real time. If you are looking to day trade and make money off short term price fluctuations you should use something like bitstamp.net which will execute your trades in real time instead of having to wait 3-5 days for them to settle.
Since we're throwing out referral links here apparently, this link will give you and I both $5 in BTC:
https://coinbase.com/?r=4fedfb2d6cbd3b0003000845&utm_campaig...