On my first ever PCB designed on computer (with mspaint!!), I forgot to mirror the printout before etching it, as well as putting TO-220 packages way too close together to fit. I was going to solder the single IC in upside down and bend the TO-220s to make them fit, but I ended redoing it properly.
The only big blunder that comes to mind recently was sending my A!tium files directly to PCBcart, instead of gerbers, after reading they accept them. "So much easier than making gerbers", I thought. They produced everything nicely, except my ground planes didn't exist! At the time I had no money or time to have them remade, so this was the result: Surprisingly the poor grounding doesn't seem to cause any image quality issues.