If this is important, I highly recommend keeping an original card around (or flashed). The NVidia (nor the AMD RX 580) card will not allow you to see the EFI boot screen with the card plugged in (the screen you see if you hold down the option key and the Apple logo).
There's hardly any special skills or knowledge needed. Upgrading only took me a few short minutes, the longest part of the process was plugging/unplugging all my connected devices. The main differences between the two are the PCIe power port positions and the lack of the annoying PCIe bar hanger latch. You can install a 10x0 series into a 2008 Mac Pro as well, but this guide specifically focuses on the 2010-2012 Mac Pros. It's lasted me well over three years and made the jump to a 2010 Mac Pro, but I finally pulled the trigger on a 1060. I included a fair amount of benchmarks to boot.
Years ago, I posted a guide on how to install a GeForce 760 or 770 into a 2008 Mac Pro.
For posterity, I've left the upgrade guide below largely intact with a few minor edits to help reflect more current information. My GPU section of the Definitive Mac Pro Upgrade Guide contains more info on this spat, as well as current information. I highly recommend AMD video cards over NVidia as this seems unlikely to change. NVidia states that it is actively being blocked from releasing drivers for its GeForce cards for 10.14.x+. Sadly, Apple and NVidia relations have seemed to have come to a head.
Updated 04/03/19: When I wrote this guide, NVidia drivers were still being released for the current version of macOS, 10.12-10.13.