In 2017, as far as being user friendly goes, probably Kega Fusion (Even though it hasn't been updated since 2010). Although Genesis Plus GX is easily the most accurate and has surpassed Kega Fusion, but unfortunately is Libretro exclusive, which means you can either use RetroArch (which is fucking terrible), or BizHawk (which isn't too bad, though if softpatching games is supported, I'd love to know!). Somebody seriously needs to port Genesis Plus GX to Windows instead of having to deal with Libretro bullshit.
I might as well give you a rundown of the other emulators too.
Regen: Older than Kega Fusion, hasn't been updated since 2009, buggy as fuck.
Exodus: Needs a super computer to run (very very slow), really more of an experiment and/or proof of concept than anything else, which is a damn shame.
BlastEm: Aiming to be as accurate as Exodus but without needing said supercomputer, this emulator could be pretty good in a few years time, but my god is the latest version fucking terrible thanks to its rudimentary GUI, I think it was originally Linux only, which might explain alot, but I'm not 100% sure on that. Either way, this one needs more time, definitely not ready for end user consumption just yet.
So yeah, just use Kega Fusion, it hasn't seen an update in years, might have some issues with newer OS, but it still fucking works and works well. Who knows, maybe Genesis Plus GX will be ported to Windows at some point, or maybe the abforementioned emulators will get some much needed updates, just gonna have to wait and see, but definitely stick with Kega for now. BizHawk is admittedly a neat emulator in its own right, even if it is mostly geared towards TAS speedruns…