I've played over 10,000 games, and I've had it happen once.  It was a real outlier, too:  Jeff Conine, a late-season addition to Florida's roster in 2003, hit 4 home runs in the LDS opener against San Francisco (two off Schmidt and one each off Herges and Worrell).   This is from a "card" which saw 5 homers in 99 plate appearances.