I have been playing with page layouts, and have carefully reproduced aspects of Bringhurst's design, including an explicit calculation of the page parameters, measure, etc. The result was achieved using the titlesec
package, placing the chapter number with the marginnote
package:
% Set the font
\defaultfontfeatures{Scale=MatchLowercase,
Mapping=tex-text}
\setmainfont[Mapping=tex-text, % E.g. -- -> en-dash
Numbers=OldStyle,
UprightFeatures={LetterSpace=-0.9},
ItalicFeatures={LetterSpace=0.9}, % To cancel -0.9 tracking
SmallCapsFeatures={LetterSpace=10.0},
]{Minion Pro}
\setkomafont{marginnote}{
\addfontfeature{UprightFeatures={LetterSpace=5}}%
\addfontfeature{ItalicFeatures={LetterSpace=5}}%
\fontsize{7pt}{9pt}\selectfont}
\setkomafont{chapternumber}{%
\fontspec[Numbers=OldStyle]{TeX Gyre Pagella}
\fontsize{72pt}{72pt}\selectfont}
\setkomafont{sectioning}{\normalfont}
\setkomafont{chapter}{\addfontfeature{UprightFeatures={LetterSpace=15.0}}}
\setkomafont{section}{\scshape}
\setkomafont{subsection}{\itshape}
% Chapters open on the right page.
\KOMAoptions{open=right}
\setlength{\parindent}{1.5em}
% Chapter formatting
\titleformat{name=\chapter}
[block]
{} % format
{\marginnote{\usekomafont{chapternumber}\thechapter}
[3\baselineskip]} % label
{0pt} % separation between label and heading
{\raggedright\usekomafont{chapter}\MakeTextUppercase} % before
[\trule] % after
\titlespacing*{\chapter}{0pt}{-\topskip}{0pt}
% Bringuest has the whole text flush left, so do not typeset the label
% independently here or the text will hang.
\titleformat{name=\section}
{\usekomafont{section}} % format
{} % label
{0pt} % separation between label and heading
{\thesection\hspace{0.5em}\MakeTextLowercase} % before
\titleformat{name=\subsection}
{\usekomafont{subsection}} % format
{} % label
{0pt} % separation between label and heading
{\raggedright{\normalfont\thesubsection}\hspace{0.5em}} % before
\titlespacing*{\section}{0pt}{0pt}{\baselineskip}
\titlespacing*{\subsection}{0pt}{\baselineskip}{\baselineskip}
The complete source is too long to post (it includes a modification to geometry
that allows page changes in the middle of a document, and explores other typographic styles) but is available on bitbucket: Exploring Typography with LaTeX. Here is the result:

As you can see, I am still having some problems with the margin-notes, but the spacing, measure, and positioning of the chapter number is almost identical to Bringhurst's design (as a demonstration of how to do this in LaTeX rather than a suggestion that one should strive to exactly reproduce this style.)
Update
Here are the same ideas applied to the memoir
class. Note: I am not fluent in memoir
and had a little bit of difficulty getting the space before the section heads properly adjusted, so the vertical alignment is not exactly correct here (and I have not adjusted the page size etc. I just blindly set the text box to match Bringhurst's measurements.)
Note also that Bringhurst places the chapter numbers at the same vertical position regardless of the title text: it does not move up or down with the first line of text so that it will always be in the same place for a reader flipping through pages in the book.
\documentclass{memoir}
\usepackage{fontspec}
\usepackage{marginnote}
\usepackage{xparse} % So we can define \trule with two optional args
\usepackage{xcolor}
% This rule will take exactly \baselinskip space, maintaining the grid. The
% raise value is the height above the next baseline. It will extend down
% thickness.
% \trule[thickness][raise]
\NewDocumentCommand\trule{O{0.4pt}O{0pt}}{
\vskip0pt\vtop to0pt{
\noindent\raisebox{#2}{\vbox{\leavevmode\hrule height#1}}}
}
\defaultfontfeatures{Scale=MatchLowercase,
Mapping=tex-text}
\setmainfont[Mapping=tex-text, % E.g. -- -> en-dash
Numbers=OldStyle,
UprightFeatures={LetterSpace=-0.9},
ItalicFeatures={LetterSpace=0.9}, % To cancel -0.9 tracking
SmallCapsFeatures={LetterSpace=10.0},
]{Minion Pro}
\usepackage{kantlipsum}
\settypeblocksize{496.32431pt}{255.8827pt}{1.25}
\makechapterstyle{Bringhurst}{%
\chapterstyle{default}
\setsecnumdepth{subsection}
\renewcommand{\chaptitlefont}
{\normalfont%
\addfontfeature{UprightFeatures={LetterSpace=15.0}}}
\renewcommand{\chapnumfont}{%
\fontspec[Numbers=OldStyle]{TeX Gyre Pagella}
\fontsize{72pt}{72pt}\selectfont
\color{black!30}}
\renewcommand*{\chapterheadstart}{}
\renewcommand*{\printchaptername}{}
\renewcommand*{\chapternamenum}{}
\renewcommand*{\printchapternum}{%
\marginnote{\chapnumfont \thechapter}[3\baselineskip]
}%
\renewcommand*{\afterchapternum}{}
\renewcommand*{\printchaptertitle}[1]{
\chaptitlefont\raggedright\MakeUppercase{##1}}
\renewcommand*{\afterchaptertitle}{\trule\vspace{\oneline}}
\setsecindent{0pt}
\setbeforesecskip{\onelineskip}
\setaftersecskip{\onelineskip}
\setsecheadstyle{\normalfont\scshape\raggedright\MakeLowercase}
\setaftersubsecskip{\onelineskip}
\setsubsecindent{0pt}
\setsubsecheadstyle{\normalfont\raggedright\itshape}
}
\frenchspacing
\begin{document}
\chapterstyle{Bringhurst}
\chapter{The Grand Design}
\section{First Principles}
\subsection{Typography exists to honour content}
Like oratory, music, dance, calligraphy -- like anything that lends
its grace to language\ldots
\kant[3]
\end{document}

textpos
package, but there must surely be a simpler way. – NVaughan Jan 1 '13 at 23:26