The link interview that broke the news says: Not surprisingly, Lloyd isn’t revealing who is headed six feet under — or if it’s one of the main family members — but he promises that he/she is a “significant character on the series” and the death “will be a moving event — and an event that has repercussions across several episodes.”

My theories, ranked by probability and maybe a little wishful thinking:
DeDe. She'll have the biggest impact on the largest number of characters. Plus, she wasn't really around all that often, so it's not like we're losing someone we're used to seeing every week.
Stella. This would mostly affect Jay, and probably come with a lot of backlash because a) what is this, Old Yeller? and b) "a significant character on the series"? Get real, you trolls.
Frank. He's getting to be That Age, and his wife's death got a whole episode. He might be worth a few more.
Jay. He'd definitely have a huge impact on the rest of the family. Ed's working on a pilot for another show. I don't like the idea, but it would definitely shake things up.
Alex. Look, I love her, but it's gotta be getting harder for them to keep nerdifying Ariel. Given Alex's history, if they're brave enough to tackle suicide on a family sitcom... well... =\

I can see Ariel Winter leaving Modern Family, also Sarah Hyland

update: Mitch and Cam are in the pics for the episode after Good Grief, and the ep description mentions Jay, Joe, Phil and Luke. So I guess those dudes are safe.