This is one of the easiest years for me. I choose Deus Ex.
For me, this is the best game of 2000, the best game of the 2000s, the best PC game ever, and -- if not for Breath of the Wild -- the best game ever. Amazing presentation and storytelling, huge replay value, outstanding level design, and, most essentially, liberating gameplay that supports player agency and rewards experimentation and outside-the-box thinking.