If your time is expensive and you will only be running a very small number of PCBs, consider using ExpressPCB's design tool, because it's easy to learn and it seamlessly connects to their board printing service. (Their service is expensive though, so this is only good if you're doing a few boards, and thus the labor you save will not be eaten up by the extra you pay per board.)
Your perception of size on screen is very different to real life. Print a paper dummy of your board. Try to avoid components with pins any denser than SOIC or 0805.
Consider putting a bridge rectifier just after your DC IN connector. Then the polarity of incoming power doesn't matter: the bridge rectifier sorts it out. (It costs you a small voltage drop, of course.) Or use a connector that's hard to get backwards, such as USB or USB micro.
Tie the RESET pin to Vcc via a resistor. A floating RESET pin may lead to random resets. (I made a PIC board that reset when you brought your hand near it.)
Make sure you put the crystal close to the CPU, and connect to it via short traces. Same with the two capacitors either side of the crystal.
Your first draft will contain errors. Expect to have to trouble-shoot these.
Tie any unused digital lines to places where you can populate LEDs for troubleshooting and diagnostic info.
You'll need to include the six-pin programmer header: your CPUs will arrive blank, without the Arduino bootloader.
When you receive your first blank board, first populate the bare minimum components needed to make the CPU run. Then connect to it from the Arduino software on your PC and burn the bootloader into it. (You'll need a programme.r) (If you've never burned a bootloader, re-burn the boot loader on your actual Arduino to make sure you have all the steps and setup correct.) Only once your CPU is running should you populate further components. This particularly applies if you're using the MOSI, MISO or SCK pins: once you connect these to other chips on your board (e.g. you're using them for SPI), you may be unable to burn the bootloader.