I think the biggest problem that a Larry games face (and one that is completely evedent in the last two) is the completely different outlook that the world has now.
Back in the days when Sierra was riding high the world saw the ugly, awkward loser trying to get laid as pitiful and pathetic and as a result Larry was portrayed as quite an obnoxious and devious character that you enjoyed seeing fail over and over again.
Nowadays with geek and nerd culture becoming mainstream and films like American Pie, Superbad, Loser etc portraying similar characters in the role of "diamond in the rough" style heroes a character like Larry just comes off as creepy and loses all of his appeal.
I believe that the idea to go with a new Larry (as in the latest games) is the right way to go, but instead of having him a smarmy pervert that is almost impossible to get behind, you have to portray him as the lovable loser who, although life keeps shitting on him, he always believes "the next time will be different".