I currently have User SEO URL\'s set to Yes in OpenCart Admin.
System -> Settings -> Store -> Server -> User SEO URL\'s
To remove index.php?route= from urls I simply recommend to edit .htaccess file.
Just add this:
RewriteCond %{THE_REQUEST} \ /index\.php\?_route_=?([^&\ ]*)
RewriteRule ^ /%1? [L,R]
I encounter no problems whatsoever. Just remember that you need to have RewriteEngine enabled. Look for this line: RewriteEngine On. If not present, past it before above code.